Mesenchymal stem cells(MSCs)can differentiate into various tissue cell types including bone,adipose,cartilage,and muscle.Among those,osteogenic differentiation of MSCs has been widely explored in many bone tissue engi...Mesenchymal stem cells(MSCs)can differentiate into various tissue cell types including bone,adipose,cartilage,and muscle.Among those,osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies.Moreover,the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing.Recently,with the gra-dual recognition of adipokines,the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism,inflammation,immune regulation,energy disorders,and bone homeostasis.At the same time,the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely.Therefore,this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs,emphasizing bone formation and bone regeneration.展开更多
Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabe...Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evi-dence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipo-genesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transform-ing growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription fac-tors, namely peroxisome proliferator-activated receptor(PPAR)-α. Recent studies have proposed downregula-tion of PPAR-α in cases of hepatic steatosis. This re-view discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD.展开更多
Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty...Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.展开更多
AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined...AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm nonalcoholic liver disease(NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score(NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic(ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis,lobular inflammation and fibrosis. RESULTS: Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08(95%CI: 1.03-1.14), 1.04(95%CI: 1.008-1.07), 1.04(95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4(95%CI: 1.09-1.8), 1.07(95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06(95%CI: 1.002-1.12), 19.86(95%CI: 2.79-141.19), 560.72(95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05(95%CI: 1.01-1.1), 1.13(95%CI: 1.04-1.22), P < 0.05]. CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.展开更多
AIM:To examine the association between obesityrelated adipokines(adiponectin,leptin,resistin,interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)and colorectal cancer(CRC)risk.METHODS:Serum levels of adipokines we...AIM:To examine the association between obesityrelated adipokines(adiponectin,leptin,resistin,interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)and colorectal cancer(CRC)risk.METHODS:Serum levels of adipokines were measured in 100 CRC patients and age-and sex-matched controls for the data analysis.Unconditional logistic regression models were used for estimating ORs and95%CIs related to each adipokine.For the metaanalysis,studies published before July 2013 available on Medline/PubMed and EMBASE were retrieved.The analysis included a total of 17 relevant studies(including the present case-control study):nine studies on adiponectin and eight on leptin.The effect sizes of ORs and 95%CIs were estimated using RevMan 5.1.Heterogeneity was evaluated using Cochran’s Q-test and I2 statistics.RESULTS:Among the five adipokines,only resistin levels were significantly higher in cases than in controls(P<0.001).The case-control study results showed no association between adiponectin and CRC and a negative association between leptin and CRC.However,the results of the meta-analysis showed a significant inverse association between adiponectin and CRC(OR=0.91,95%CI:0.83-1.00,P=0.04)and no association between CRC and leptin.After stratification by study design,an inverse association between adiponectin and CRC was observed in prospective studies only(OR=0.90,95%CI:0.82-0.99,P=0.03),whereas the association between leptin and CRC was inconsistent(prospective studies:OR=1.14,95%CI:1.02-1.27,P=0.02 and retrospective studies:OR=0.47,95%CI:0.29-0.74,P=0.001).The associations of resistin and TNF-αwith CRC risk were positive,but no association was observed for IL-6.CONCLUSION:Our results suggest a negative association of leptin,positive associations of resistin and TNF-α,and null associations of adiponectin and IL-6with CRC.However,further studies with larger number of prospective approaches are needed.展开更多
AIM:To investigate serum adipokine levels in inflammatory bowel disease(IBD)patients before treatment and after achieving clinical remission.METHODS:Serum concentrations of six adipokines(tissue growth factor-β1,adip...AIM:To investigate serum adipokine levels in inflammatory bowel disease(IBD)patients before treatment and after achieving clinical remission.METHODS:Serum concentrations of six adipokines(tissue growth factor-β1,adiponectin,leptin,chemerin,resistin,and visfatin)were studied in 40 subjects with active IBD[24 subjects with Crohn’s disease(CD)and in 16 subjects with ulcerative colitis(UC)]before and after three months of therapy with corticosteroids and/or azathioprine.Clinical diagnoses were based on ileocolonoscopy,computed tomography or magnetic resonance enterography and histological examination of mucosal biopsies sampled during endoscopy.Serum levels of adipokines were assessed by an indirect enzyme-linked immunosorbent assay.The control group was comprised of 16 age-and sex-matched healthyvolunteers.RESULTS:Baseline leptin concentrations were significantly decreased in both types of IBD compared to controls(8.0±9.1 in CD and 8.6±6.3 in UC vs 16.5±10.1 ng/mL in controls;P<0.05),and significantly increased after treatment only in subjects with CD(14.9±15.1 ng/mL;P<0.05).Baseline serum resistin concentrations were significantly higher in CD(19.3±12.5ng/mL;P<0.05)and UC subjects(23.2±11.0 ng/mL;P<0.05)than in healthy controls(10.7±1.1 ng/mL).Treatment induced a decrease in the serum resistin concentration only in UC subjects(14.5±4.0 ng/mL;P<0.05).Baseline serum concentrations of visfatin were significantly higher in subjects with CD(23.2±3.2ng/mL;P<0.05)and UC(18.8±5.3 ng/mL;P<0.05)than in healthy controls(14.1±5.3 ng/mL).Treatment induced a decrease in the serum visfatin concentrations only in CD subjects(20.4±4.8 ng/mL;P<0.05).Serum levels of adiponectin,chemerin and tissue growth factor-β1 did not differ between CD and UC subjects compared to healthy controls and also were not altered by anti-inflammatory therapy.Clinical indices of IBD activity did not correlate with adipokine levels.CONCLUSION:IBD modulates serum adipokine levels by increasing resistin and visfatin release and suppressing leptin production.展开更多
AIM:to analyze adipokine concentrations,insulin resistance and hepatic expression of suppressor of cytokine signaling 3(SOCS-3)in patients with chronic hepatitis C genotype 1 with normal body weight,glucose and lipid ...AIM:to analyze adipokine concentrations,insulin resistance and hepatic expression of suppressor of cytokine signaling 3(SOCS-3)in patients with chronic hepatitis C genotype 1 with normal body weight,glucose and lipid profile.METHODS:The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects.Total levels of adiponectin,leptin,resistin,visfatin,omentin,osteopontin and insulin were measured using an ELISA kit.The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method.RESULTS:Homeostasis model assessment for insulin resistance(HOMA-IR)values were significantly higher in hepatitis C virus(HCV)infected patients without metabolic disorders compared to healthy controls(2.24 vs 0.59,P=0.0003).Hepatic steatosis was observed in 32.2%of patients with HCV infection and was found in patients with increased HOMA-IR index(2.81 vs1.99,P=0.05)and reduced adiponectin level(5.96vs 8.37,P=0.04).Inflammatory activity(G≥2)was related to increased osteopontin concentration(34.04vs 23.35,P=0.03).Advanced liver fibrosis(S≥2)was associated with increased levels of omentin and osteopontin(436.94 vs 360.09,P=0.03 and 32.84 vs20.29,P=0.03)and reduced resistin concentration(1.40 vs 1.74,P=0.047).No correlations were reported between adipokine profile,HOMA-IR values and hepatic expression of the SOCS-3 gene.CONCLUSION:We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself.Some adipokines appear to be biochemical markers of steatosis,inflammation and fibrosis in patients with chronic HCV infection.展开更多
AIM:To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2cells.METHODS:The mRNA expression of farnesoid X receptor(FXR),per...AIM:To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2cells.METHODS:The mRNA expression of farnesoid X receptor(FXR),peroxisome proliferator-activated receptor-gamma 2(PPAR-γ2),adiponectin,leptin,resistin,adiponectin receptor 1(AdipoR1),adiponectin receptor2(AdipoR2),and the long isoform of leptin receptor(OB-Rb)and protein levels of adiponectin,leptin,andresistin were determined using fluorescent real-time PCR and enzyme linked immunosorbent assay,respectively,on days 0,2,4,6,and 8 during the differentiation of 3T3-L1 preadipocytes exposed to GW4064.Moreover,mRNA expression of AdipoR2 and OB-Rb was also examined using fluorescent real-time PCR at 0,12,24,and 48 h in HepG2 cells treated with GW4064.RESULTS:The mRNA expression of FXR,PPAR-γ2,adiponectin,leptin,resistin,AdipoR1,AdipoR2,and OB-Rb and protein levels of adiponectin,leptin,and resistin increased along with differentiation of 3T3-L1preadipocytes(P<0.05 for all).The mRNA expression of FXR,PPAR-γ2,adiponectin,leptin,and AdipoR2in 3T3-L1 preadipocytes,and AdipoR2 and OB-Rb in HepG2 cells was significantly increased after treatment with GW4064,when compared with the control group(P<0.05 for all).A similar trend was observed for protein levels of adipokines(including adiponectin,leptin and resistin).However,the expression of resistin,AdipoR1,and OB-Rb in 3T3-L1 cells did not change after treatment with GW4064.CONCLUSION:The FXR agonist through regulating,at least partially,the expression of adipokines and their receptors could offer an innovative way for counteracting the progress of metabolic diseases such as nonalcoholic fatty liver disease.展开更多
Osteoarthritis(OA)is one of the most common degenerative joint diseases in aging population.Obesity is an important risk factor for initiation and progression of OA.It is accepted that excess body weight may lead to c...Osteoarthritis(OA)is one of the most common degenerative joint diseases in aging population.Obesity is an important risk factor for initiation and progression of OA.It is accepted that excess body weight may lead to cartilage degeneration by increasing the mechanical forces across weight-bearing joints.However,emerging data suggest that additional metabolic factors released mainly by white adipose tissue may also be responsible for the high prevalence of OA among obese people.Adipocyte-derived molecules‘‘adipokines’’have prompt much interest in OA pathophysiological research over the past decade since they play an important role in cartilage and bone homeostasis.Therefore,the aim of this review is to summarize the current knowledge on the role of adipokines including leptin,adiponectin,visfatin and resistin in OA and their potential to be used as biomarkers for earlier diagnosis,classifying disease severity,monitoring disease progression,and testing pharmacological interventions for OA.In OA patients,leptin,visfatin and resistin showed increased production whereas adiponectin showed decreased production.Leptin and adiponectin are far more studied than visfatin and resistin.Importantly,altered adipokine levels also contribute to a wide range of diseases.Further experiments are still crucial for understanding the relationship between adipokines and OA.展开更多
AIM:To investigate the adipokine levels of leptin,adiponectin,resistin,visfatin,retinol-binding protein 4(RBP4),apelin in alcoholic liver cirrhosis(ALC).METHODS:Forty non-diabetic ALC patients[median age:59 years,male...AIM:To investigate the adipokine levels of leptin,adiponectin,resistin,visfatin,retinol-binding protein 4(RBP4),apelin in alcoholic liver cirrhosis(ALC).METHODS:Forty non-diabetic ALC patients[median age:59 years,males:35(87.5%),Child-Pugh(CP)score:median 7(5-12),CP A/B/C:18/10/12,Model for End-stage Liver Disease(MELD):median 10(6-25),follow-up:median 32.5 mo(10-43)]were prospectively included.The serum adipokine levels were estimated in duplicate by ELISA.Somatometric characteristics were assessed with tetrapolar bioelectrical impedance analysis.Pearson’s rank correlation coefficient was used to assess possible associations with adipokine levels.Univariate and multivariate Cox regression analysis was used to determine independent predictors for overallsurvival.RESULTS:Body mass index:median 25.9(range:20.1-39.3),fat:23.4%(7.6-42.1),fat mass:17.8(5.49-45.4),free fat mass:56.1(39.6-74.4),total body water(TBW):40.6(29.8-58.8).Leptin and visfatin levels were positively associated with fat mass(P<0.001/P=0.027,respectively)and RBP4 with TBW(P=0.025).Median adiponectin levels were significantly higher in CPC compared to CPA(CPA:7.99±14.07,CPB:7.66±3.48,CPC:25.73±26.8,P=0.04),whereas median RBP4 and apelin levels decreased across the spectrum of disease severity(P=0.006/P=0.034,respectively).Following adjustment for fat mass,visfatin and adiponectin levels were significantly increased from CPA to CPC(both P<0.001),whereas an inverse correlation was observed for both RBP4 and apelin(both P<0.001).In the multivariate Cox regression analysis,only MELD had an independent association with overall survival(HR=1.53,95%CI:1.05-2.32;P=0.029).CONCLUSION:Adipokines are associated with deteriorating liver function in a complex manner in patients with alcoholic liver cirrhosis.展开更多
The cardioprotective effects of lipid-lowering drugs have been primarily attributed to their effects on blood lipid metabolism.However,emerging evidence indicates that lipid-lowering drugs also modulate the synthesis ...The cardioprotective effects of lipid-lowering drugs have been primarily attributed to their effects on blood lipid metabolism.However,emerging evidence indicates that lipid-lowering drugs also modulate the synthesis and secretion of adipose tissue-secreted proteins referred to as adipokines.Adipokines influence energy homeostasis and metabolism and have also been shown to modulate the vascular inflammatory cascade.The purpose of this review will be to examine the reported effects of commonly used lipid-lowering drugs(statins,fibrates,niacin and omega-3-fatty acids) on the circulating concentrations of leptin,adiponectin,tumor necrosisfactor-α(TNF-α),Retinol binding protein 4(RBP4) and resistin.Overall,the lipid-lowering drugs reviewed have minimal effects on leptin and resistin concentrations.Conversely,circulating adiponectin concentrations are consistently increased by each lipid-lowering drug reviewed with the greatest effects produced by niacin.Studies that have examined the effects of statins,niacin and omega-3-fatty acids on TNF-α demonstrate that these agents have little effect on circulating TNF-α concentrations.Niacin and fibrates appear to lower RBP4 but not resistin concentrations.The results of the available studies suggest that a strong relationship exists between pharmacological reductions in blood lipids and adiponectin that is not obvious for other adipokines reviewed.展开更多
The traditional perception of adipose tissue as a storage organ of fatty acids has been replaced by the notion that adipose tissue is an active endocrine organ, releasing various adipokines that are involved in the pa...The traditional perception of adipose tissue as a storage organ of fatty acids has been replaced by the notion that adipose tissue is an active endocrine organ, releasing various adipokines that are involved in the pathogenesis of obesity-related metabolic disturbances. Obesity is a well-known risk factor for atherosclerosis, and accelerates atherosclerosis by many mechanisms such as increase in blood pressure and glucose level, abnormal lipid profiles, and systemic inflammation. Furthermore, growing evidence suggests that some adipokines directly mediate the process of atherosclerosis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in vessel walls. In obese patients, the secretion and coordination of such adipokines is abnormal, and the secretion of specific adipokines increases or decreases. Accordingly, the discovery of new adipokines and elucidation of their functions might lead to a new treatment strategy for metabolic disorders related to obesity, including cardiovascular diseases.展开更多
AIM: To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein...AIM: To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein (HSCRP). METHODS: A case-control study was performed. Cases were 44 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (≥ 5%). Other causes of chronic liver disease were ruled out. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1-basis) with thecases on age, gender, pubertal stage and as closely as possible on body mass index-SD score. All participants underwent clinical examination, laboratory tests, and whole body (WB) and lumbar spine (LS) BMD by dual energy X-ray absorptiometry. BMDZ-scores were calcu- lated using race and gender specific LMS curves. RESULTS: Obese children with NAFLD had a significantly lower LS BMDZ-score than those without NAFLD [mean, 0.55 (95%CI: 0.23-0.86) vs 1.29 (95%CI: 0.95-1.63); P < 0.01]. WB BMD Z-score was also decreased in obese children with NAFLD compared to obese children with no NAFLD, though borderline significance was observed [1.55 (95%CI: 1.23-1.87) vs 1.95 (95%CI: 1.67-2.10); P = 0.06]. Children with NAFLD had significantly higher HSCRP, lower adiponectin, but similar leptin levels. Thirty five of the 44 children with MRI-diagnosed NAFLD underwent liver biopsy. Among the children with biopsy-proven NAFLD, 20 (57%) had nonalcoholic steatohepatitis (NASH), while 15 (43%) no NASH. Compared to children without NASH, those with NASH had a significantly lower LS BMD Z-score [mean, 0.27 (95%CI: -0.17-0.71) vs 0.75 (95%CI: 0.13-1.39); P < 0.05] as well as a significantly lower WB BMD Z-score [1.38 (95%CI: 0.89-1.17) vs 1.93 (95%CI: 1.32-2.36); P < 0.05]. In multiple regression analysis, NASH (standardized β coefficient, -0.272; P < 0.01) and HSCRP (standardized β coefficient, -0.192; P < 0.05) were significantly and independently associated with LS BMD Z-score. Similar results were obtained when NAFLD (instead of NASH) was included in the model. WB BMD Z-scores were significantly and independently associated with NASH (standardized β coefficient, -0.248;P < 0.05) and fat mass (standardized β coefficient, -0.224;P < 0.05). CONCLUSION: This study reveals that NAFLD is associated with low BMD in obese children, and that systemic, low-grade inflammation may accelerate loss of bone mass in patients with NAFLD.展开更多
Development of type 2 diabetes has been linked to β-cell failure coupled with insulin resistance and obesity. Adipose tissue, known as the fat store, secretes a number of hormones and proteins collectively termed adi...Development of type 2 diabetes has been linked to β-cell failure coupled with insulin resistance and obesity. Adipose tissue, known as the fat store, secretes a number of hormones and proteins collectively termed adipokines some of which regulate insulin sensitivity. Dysregulation in the secretion of adipokines has been linked to insulin resistance and type 2 diabetes. In this review, we sum-marized evidence of the role of adipokines with focus on leptin, adiponectin, adipsin, visfatin and apelin in the pathogenesis of type 2 diabetes and discussed the potential of saponins to modify the ill-regulated adipokines secretions, which could promote the use of this class of phytochemicals as potential antidiabetics agents.展开更多
Atherosclerotic cardiovascular disease is a major health problem around the world.Obesity is a primary risk factor for atherosclerosis and is associated with increased morbidity and mortality of cardiovascular disease...Atherosclerotic cardiovascular disease is a major health problem around the world.Obesity is a primary risk factor for atherosclerosis and is associated with increased morbidity and mortality of cardiovascular diseases.However,the precise molecular pathways underlying this close association remain poorly understood.Adipokines are cytokines,chemokines and hormones secreted by adipose tissue that couple the regulation of lipid accumulation,inflammation,and atherogenesis,and therefore serve to link obesity with cardiovascular disorders.Obesity-related disorders including metabolic syndrome,diabetes,atherosclerosis,hypertension,and coronary artery disease are associated with dysregulated adipokine(s) expression.Recent studies demonstrate the proinflammatory effects as well as atherogenic properties of adipokines.Adipokines also participate in the regulation of endothelial function,which is an early event in atherosclerosis.By contrast,adiponectin,an adipocyte-derived hormone,exerts anti-inflammatory,anti-atherogenic and vascular protective effects.Furthermore,there is an interactive association among adipokines,by which adipokines reciprocally regulate each other’s expression.Understanding this interplay may reveal plausible mechanisms for treating atherosclerosis and coronary heart disease by modulating adipokine(s) expression.In this review,we discuss insights into the role and the therapeutic potential of adipokines as mediators of atherosclerosis.展开更多
Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes assoc...Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding ofthe mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.展开更多
BACKGROUNDGhrelin is an adipokine that plays an important role in energy balance. Expressionof ghrelin and ghrelin receptor has been investigated in different tissues andtumors. Studies regarding expression of ghrelin...BACKGROUNDGhrelin is an adipokine that plays an important role in energy balance. Expressionof ghrelin and ghrelin receptor has been investigated in different tissues andtumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectaltumors are scarce and no data on expression of ghrelin and its receptor incolorectal adenomas has been published. Ghrelin and ghrelin receptor werehighly expressed in colon carcinoma cells while expression was decreased in lessdifferentiated tumors, presuming that ghrelin might be important in early phasesof tumorigenesis.AIMTo investigate the expression of ghrelin and ghrelin receptor in human colorectaladenomas and adjacent colorectal tissue.METHODSIn this prospective study (conducted from June 2015 until May 2019) we included92 patients (64 male and 28 female) who underwent polypectomy for colorectaladenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. After endoscopicremoval of colorectal adenoma, an additional sample of colon mucosa in theproximity of the adenoma was collected for pathohistological analysis. Adenomaswere graded according to the stage of dysplasia, and ghrelin and ghrelin receptorexpression were determined immunohistochemically in both adenoma andadjacent colon tissue using the polyclonal antibody for ghrelin (ab150514,ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAMInc, Cambridge, United States). Categorical and nominal variables were describedthrough frequencies and proportions and the difference between specific groupswere analyzed with Fisher’s and Fisher-Freeman-Halton’s method respectively.Spearman's rank correlation coefficient was determined for correlation ofexpression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissuewith the grade of adenoma dysplasia.RESULTSAmong 92 patients with colorectal adenoma 43 had adenomas with high-gradedysplasia (46.7%). High expression of ghrelin was 7 times more common in highgradeadenoma compared to low-grade adenomas (13.95% to 2.04%, P = 0.048),while the expression of ghrelin in adjacent colon tissue was low. We found nocorrelation between ghrelin receptor expression in adenoma and adjacent colontissue and the grade of colorectal adenoma dysplasia. The most significantcorrelation was found between ghrelin and ghrelin receptor expression inadenomas with high-grade dysplasia (rho = 0.519, P < 0.001).CONCLUSIONGhrelin and ghrelin receptor are expressed in colorectal adenoma and adjacenttissue with ghrelin expression being more pronounced in high grade dysplasia asa possible consequence of increased local synthesis.展开更多
Aim Adipose tissue releases adipokines that play important roles in metabolic and cardiocerebro- vascu- lar homeostasis. This study was to discover novel adipokines using caloric restriction model. Methods Adipokine c...Aim Adipose tissue releases adipokines that play important roles in metabolic and cardiocerebro- vascu- lar homeostasis. This study was to discover novel adipokines using caloric restriction model. Methods Adipokine candidates were captured by gene array and bioinformatics analysis and verified by preparation of recombinant pro- tein and antibody. Results We established a potential secreted protein database containing 208 genes and identi- fied a novel adipokine, Subfatin, that was the highest expressed in subcutaneous fat of both rodents and humans a- mong 15 detected tissues. The secreted mammalian Subfatin was a glycosylated protein. Subfatin was located dif- fusely throughout the adipose tissue except lipid droplets, with comparable expression between adipocytes and stro- real cells, but much lower expression in macrophages than adipocytes. Subfatin was downregulated in white adipose tissue of caloric restriction rats, whereas dramatically upregulated during white adipocyte differentiation as well as in white adipose tissue of diet-induced obese mice. Subfatin was annotated as Meteorin-like （Metrnl） in public data- bases, a similar transcript of Meteorin （Metrn, also known as glial cell differentiation regulator）. Meteorin dis- played a brain-specific expression and was scarce in various adipose tissues, in contrast to the tissue expression pat- terns of Subfatin. Conclusions Subfatin is a novel adipokine regulated by adipogenesis and obesity, with tissue distribution different from its homologue Meteorin.展开更多
Growth rate affects adipose tissue development and variations in growth rate may potentially impact adipokine expression. Samples of subcutaneous (SQ) and perirenal (PR) adipose tissues and longissimus muscle were col...Growth rate affects adipose tissue development and variations in growth rate may potentially impact adipokine expression. Samples of subcutaneous (SQ) and perirenal (PR) adipose tissues and longissimus muscle were collected at day 21 of age from the fastest and slowest growing piglets within seven litters. Reverse transcription and real-time PCR were used to quantify adipokine mRNA abundance. Leptin, adiponectin, tumor necrosis factor α (TNFα ) and lipoprotein lipase (LPL) mRNA abundance were lower in SQ from slow growing piglets (SGP) than in fast growing piglets (FGP, P α gene expression were reduced in PR from SGP in comparison to FGP (P β (IL1β), IL15 and LPL were increased in the longissimus of SGP relative to FGP (P < 0.05). Analysis of mRNA abundance for these adipokines within adipose tissue at day 21 of age demonstrated that the effect of growth rate on adipokine expression varies among different adipokines and the internal and external sites of adipose tissue deposition (PR versus SQ). The increase in longissimus expression of LPL and IL15 suggests that nutrient partitioning for energy use may be greater in the skeletal muscle of the SGP.展开更多
基金the Changzhou Science&Technology Program,No.CJ20210104,CJ20220120,and CJ20210005Qinghai Province Health System Guidance Plan Project,No.2022-wjzdx-106+1 种基金Young Talent Development Plan of Changzhou Health commission,No.CZQM2020059Top Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project,No.2022CZBJ059 and 2022CZBJ061.
文摘Mesenchymal stem cells(MSCs)can differentiate into various tissue cell types including bone,adipose,cartilage,and muscle.Among those,osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies.Moreover,the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing.Recently,with the gra-dual recognition of adipokines,the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism,inflammation,immune regulation,energy disorders,and bone homeostasis.At the same time,the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely.Therefore,this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs,emphasizing bone formation and bone regeneration.
文摘Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evi-dence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipo-genesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transform-ing growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription fac-tors, namely peroxisome proliferator-activated receptor(PPAR)-α. Recent studies have proposed downregula-tion of PPAR-α in cases of hepatic steatosis. This re-view discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD.
文摘Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.
文摘AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm nonalcoholic liver disease(NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score(NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic(ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis,lobular inflammation and fibrosis. RESULTS: Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08(95%CI: 1.03-1.14), 1.04(95%CI: 1.008-1.07), 1.04(95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4(95%CI: 1.09-1.8), 1.07(95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06(95%CI: 1.002-1.12), 19.86(95%CI: 2.79-141.19), 560.72(95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05(95%CI: 1.01-1.1), 1.13(95%CI: 1.04-1.22), P < 0.05]. CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.
基金Supported by Korean Ministry of Health and Welfare through the National R and C Program of Cancer Control(1020420)2010 Research Grant from Kangwon National University
文摘AIM:To examine the association between obesityrelated adipokines(adiponectin,leptin,resistin,interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)and colorectal cancer(CRC)risk.METHODS:Serum levels of adipokines were measured in 100 CRC patients and age-and sex-matched controls for the data analysis.Unconditional logistic regression models were used for estimating ORs and95%CIs related to each adipokine.For the metaanalysis,studies published before July 2013 available on Medline/PubMed and EMBASE were retrieved.The analysis included a total of 17 relevant studies(including the present case-control study):nine studies on adiponectin and eight on leptin.The effect sizes of ORs and 95%CIs were estimated using RevMan 5.1.Heterogeneity was evaluated using Cochran’s Q-test and I2 statistics.RESULTS:Among the five adipokines,only resistin levels were significantly higher in cases than in controls(P<0.001).The case-control study results showed no association between adiponectin and CRC and a negative association between leptin and CRC.However,the results of the meta-analysis showed a significant inverse association between adiponectin and CRC(OR=0.91,95%CI:0.83-1.00,P=0.04)and no association between CRC and leptin.After stratification by study design,an inverse association between adiponectin and CRC was observed in prospective studies only(OR=0.90,95%CI:0.82-0.99,P=0.03),whereas the association between leptin and CRC was inconsistent(prospective studies:OR=1.14,95%CI:1.02-1.27,P=0.02 and retrospective studies:OR=0.47,95%CI:0.29-0.74,P=0.001).The associations of resistin and TNF-αwith CRC risk were positive,but no association was observed for IL-6.CONCLUSION:Our results suggest a negative association of leptin,positive associations of resistin and TNF-α,and null associations of adiponectin and IL-6with CRC.However,further studies with larger number of prospective approaches are needed.
基金Supported by a grant from the Medical University of Silesia,No.KNW-1-119/P/1/0
文摘AIM:To investigate serum adipokine levels in inflammatory bowel disease(IBD)patients before treatment and after achieving clinical remission.METHODS:Serum concentrations of six adipokines(tissue growth factor-β1,adiponectin,leptin,chemerin,resistin,and visfatin)were studied in 40 subjects with active IBD[24 subjects with Crohn’s disease(CD)and in 16 subjects with ulcerative colitis(UC)]before and after three months of therapy with corticosteroids and/or azathioprine.Clinical diagnoses were based on ileocolonoscopy,computed tomography or magnetic resonance enterography and histological examination of mucosal biopsies sampled during endoscopy.Serum levels of adipokines were assessed by an indirect enzyme-linked immunosorbent assay.The control group was comprised of 16 age-and sex-matched healthyvolunteers.RESULTS:Baseline leptin concentrations were significantly decreased in both types of IBD compared to controls(8.0±9.1 in CD and 8.6±6.3 in UC vs 16.5±10.1 ng/mL in controls;P<0.05),and significantly increased after treatment only in subjects with CD(14.9±15.1 ng/mL;P<0.05).Baseline serum resistin concentrations were significantly higher in CD(19.3±12.5ng/mL;P<0.05)and UC subjects(23.2±11.0 ng/mL;P<0.05)than in healthy controls(10.7±1.1 ng/mL).Treatment induced a decrease in the serum resistin concentration only in UC subjects(14.5±4.0 ng/mL;P<0.05).Baseline serum concentrations of visfatin were significantly higher in subjects with CD(23.2±3.2ng/mL;P<0.05)and UC(18.8±5.3 ng/mL;P<0.05)than in healthy controls(14.1±5.3 ng/mL).Treatment induced a decrease in the serum visfatin concentrations only in CD subjects(20.4±4.8 ng/mL;P<0.05).Serum levels of adiponectin,chemerin and tissue growth factor-β1 did not differ between CD and UC subjects compared to healthy controls and also were not altered by anti-inflammatory therapy.Clinical indices of IBD activity did not correlate with adipokine levels.CONCLUSION:IBD modulates serum adipokine levels by increasing resistin and visfatin release and suppressing leptin production.
基金Supported by Medical University,Lodz,Poland,No.502-03/1-117-01/502-14-061
文摘AIM:to analyze adipokine concentrations,insulin resistance and hepatic expression of suppressor of cytokine signaling 3(SOCS-3)in patients with chronic hepatitis C genotype 1 with normal body weight,glucose and lipid profile.METHODS:The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects.Total levels of adiponectin,leptin,resistin,visfatin,omentin,osteopontin and insulin were measured using an ELISA kit.The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method.RESULTS:Homeostasis model assessment for insulin resistance(HOMA-IR)values were significantly higher in hepatitis C virus(HCV)infected patients without metabolic disorders compared to healthy controls(2.24 vs 0.59,P=0.0003).Hepatic steatosis was observed in 32.2%of patients with HCV infection and was found in patients with increased HOMA-IR index(2.81 vs1.99,P=0.05)and reduced adiponectin level(5.96vs 8.37,P=0.04).Inflammatory activity(G≥2)was related to increased osteopontin concentration(34.04vs 23.35,P=0.03).Advanced liver fibrosis(S≥2)was associated with increased levels of omentin and osteopontin(436.94 vs 360.09,P=0.03 and 32.84 vs20.29,P=0.03)and reduced resistin concentration(1.40 vs 1.74,P=0.047).No correlations were reported between adipokine profile,HOMA-IR values and hepatic expression of the SOCS-3 gene.CONCLUSION:We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself.Some adipokines appear to be biochemical markers of steatosis,inflammation and fibrosis in patients with chronic HCV infection.
基金Supported by Guangdong Provincial Science and Technology Projects,No.2011B050400009Scientific Research Projects of Hubei Province Education Department,No.B2014055
文摘AIM:To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2cells.METHODS:The mRNA expression of farnesoid X receptor(FXR),peroxisome proliferator-activated receptor-gamma 2(PPAR-γ2),adiponectin,leptin,resistin,adiponectin receptor 1(AdipoR1),adiponectin receptor2(AdipoR2),and the long isoform of leptin receptor(OB-Rb)and protein levels of adiponectin,leptin,andresistin were determined using fluorescent real-time PCR and enzyme linked immunosorbent assay,respectively,on days 0,2,4,6,and 8 during the differentiation of 3T3-L1 preadipocytes exposed to GW4064.Moreover,mRNA expression of AdipoR2 and OB-Rb was also examined using fluorescent real-time PCR at 0,12,24,and 48 h in HepG2 cells treated with GW4064.RESULTS:The mRNA expression of FXR,PPAR-γ2,adiponectin,leptin,resistin,AdipoR1,AdipoR2,and OB-Rb and protein levels of adiponectin,leptin,and resistin increased along with differentiation of 3T3-L1preadipocytes(P<0.05 for all).The mRNA expression of FXR,PPAR-γ2,adiponectin,leptin,and AdipoR2in 3T3-L1 preadipocytes,and AdipoR2 and OB-Rb in HepG2 cells was significantly increased after treatment with GW4064,when compared with the control group(P<0.05 for all).A similar trend was observed for protein levels of adipokines(including adiponectin,leptin and resistin).However,the expression of resistin,AdipoR1,and OB-Rb in 3T3-L1 cells did not change after treatment with GW4064.CONCLUSION:The FXR agonist through regulating,at least partially,the expression of adipokines and their receptors could offer an innovative way for counteracting the progress of metabolic diseases such as nonalcoholic fatty liver disease.
基金Supported by Post-Doctoral Fellowship Research Grant from Ratchadaphiseksomphot Endowment FundChulalongkorn University,Ratchadapiseksompotch Fund+1 种基金Faculty of Medicine,Chulalongkorn University,Thailand Research Fundthe Commission of Higher Education
文摘Osteoarthritis(OA)is one of the most common degenerative joint diseases in aging population.Obesity is an important risk factor for initiation and progression of OA.It is accepted that excess body weight may lead to cartilage degeneration by increasing the mechanical forces across weight-bearing joints.However,emerging data suggest that additional metabolic factors released mainly by white adipose tissue may also be responsible for the high prevalence of OA among obese people.Adipocyte-derived molecules‘‘adipokines’’have prompt much interest in OA pathophysiological research over the past decade since they play an important role in cartilage and bone homeostasis.Therefore,the aim of this review is to summarize the current knowledge on the role of adipokines including leptin,adiponectin,visfatin and resistin in OA and their potential to be used as biomarkers for earlier diagnosis,classifying disease severity,monitoring disease progression,and testing pharmacological interventions for OA.In OA patients,leptin,visfatin and resistin showed increased production whereas adiponectin showed decreased production.Leptin and adiponectin are far more studied than visfatin and resistin.Importantly,altered adipokine levels also contribute to a wide range of diseases.Further experiments are still crucial for understanding the relationship between adipokines and OA.
文摘AIM:To investigate the adipokine levels of leptin,adiponectin,resistin,visfatin,retinol-binding protein 4(RBP4),apelin in alcoholic liver cirrhosis(ALC).METHODS:Forty non-diabetic ALC patients[median age:59 years,males:35(87.5%),Child-Pugh(CP)score:median 7(5-12),CP A/B/C:18/10/12,Model for End-stage Liver Disease(MELD):median 10(6-25),follow-up:median 32.5 mo(10-43)]were prospectively included.The serum adipokine levels were estimated in duplicate by ELISA.Somatometric characteristics were assessed with tetrapolar bioelectrical impedance analysis.Pearson’s rank correlation coefficient was used to assess possible associations with adipokine levels.Univariate and multivariate Cox regression analysis was used to determine independent predictors for overallsurvival.RESULTS:Body mass index:median 25.9(range:20.1-39.3),fat:23.4%(7.6-42.1),fat mass:17.8(5.49-45.4),free fat mass:56.1(39.6-74.4),total body water(TBW):40.6(29.8-58.8).Leptin and visfatin levels were positively associated with fat mass(P<0.001/P=0.027,respectively)and RBP4 with TBW(P=0.025).Median adiponectin levels were significantly higher in CPC compared to CPA(CPA:7.99±14.07,CPB:7.66±3.48,CPC:25.73±26.8,P=0.04),whereas median RBP4 and apelin levels decreased across the spectrum of disease severity(P=0.006/P=0.034,respectively).Following adjustment for fat mass,visfatin and adiponectin levels were significantly increased from CPA to CPC(both P<0.001),whereas an inverse correlation was observed for both RBP4 and apelin(both P<0.001).In the multivariate Cox regression analysis,only MELD had an independent association with overall survival(HR=1.53,95%CI:1.05-2.32;P=0.029).CONCLUSION:Adipokines are associated with deteriorating liver function in a complex manner in patients with alcoholic liver cirrhosis.
基金Supported by Boshell Diabetes and Metabolic Diseases Research Program
文摘The cardioprotective effects of lipid-lowering drugs have been primarily attributed to their effects on blood lipid metabolism.However,emerging evidence indicates that lipid-lowering drugs also modulate the synthesis and secretion of adipose tissue-secreted proteins referred to as adipokines.Adipokines influence energy homeostasis and metabolism and have also been shown to modulate the vascular inflammatory cascade.The purpose of this review will be to examine the reported effects of commonly used lipid-lowering drugs(statins,fibrates,niacin and omega-3-fatty acids) on the circulating concentrations of leptin,adiponectin,tumor necrosisfactor-α(TNF-α),Retinol binding protein 4(RBP4) and resistin.Overall,the lipid-lowering drugs reviewed have minimal effects on leptin and resistin concentrations.Conversely,circulating adiponectin concentrations are consistently increased by each lipid-lowering drug reviewed with the greatest effects produced by niacin.Studies that have examined the effects of statins,niacin and omega-3-fatty acids on TNF-α demonstrate that these agents have little effect on circulating TNF-α concentrations.Niacin and fibrates appear to lower RBP4 but not resistin concentrations.The results of the available studies suggest that a strong relationship exists between pharmacological reductions in blood lipids and adiponectin that is not obvious for other adipokines reviewed.
文摘The traditional perception of adipose tissue as a storage organ of fatty acids has been replaced by the notion that adipose tissue is an active endocrine organ, releasing various adipokines that are involved in the pathogenesis of obesity-related metabolic disturbances. Obesity is a well-known risk factor for atherosclerosis, and accelerates atherosclerosis by many mechanisms such as increase in blood pressure and glucose level, abnormal lipid profiles, and systemic inflammation. Furthermore, growing evidence suggests that some adipokines directly mediate the process of atherosclerosis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in vessel walls. In obese patients, the secretion and coordination of such adipokines is abnormal, and the secretion of specific adipokines increases or decreases. Accordingly, the discovery of new adipokines and elucidation of their functions might lead to a new treatment strategy for metabolic disorders related to obesity, including cardiovascular diseases.
基金Supported by A Grant from Sapienza University of Rome,Progetti di Ricerca Universitaria 2010-2011
文摘AIM: To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein (HSCRP). METHODS: A case-control study was performed. Cases were 44 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (≥ 5%). Other causes of chronic liver disease were ruled out. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1-basis) with thecases on age, gender, pubertal stage and as closely as possible on body mass index-SD score. All participants underwent clinical examination, laboratory tests, and whole body (WB) and lumbar spine (LS) BMD by dual energy X-ray absorptiometry. BMDZ-scores were calcu- lated using race and gender specific LMS curves. RESULTS: Obese children with NAFLD had a significantly lower LS BMDZ-score than those without NAFLD [mean, 0.55 (95%CI: 0.23-0.86) vs 1.29 (95%CI: 0.95-1.63); P < 0.01]. WB BMD Z-score was also decreased in obese children with NAFLD compared to obese children with no NAFLD, though borderline significance was observed [1.55 (95%CI: 1.23-1.87) vs 1.95 (95%CI: 1.67-2.10); P = 0.06]. Children with NAFLD had significantly higher HSCRP, lower adiponectin, but similar leptin levels. Thirty five of the 44 children with MRI-diagnosed NAFLD underwent liver biopsy. Among the children with biopsy-proven NAFLD, 20 (57%) had nonalcoholic steatohepatitis (NASH), while 15 (43%) no NASH. Compared to children without NASH, those with NASH had a significantly lower LS BMD Z-score [mean, 0.27 (95%CI: -0.17-0.71) vs 0.75 (95%CI: 0.13-1.39); P < 0.05] as well as a significantly lower WB BMD Z-score [1.38 (95%CI: 0.89-1.17) vs 1.93 (95%CI: 1.32-2.36); P < 0.05]. In multiple regression analysis, NASH (standardized β coefficient, -0.272; P < 0.01) and HSCRP (standardized β coefficient, -0.192; P < 0.05) were significantly and independently associated with LS BMD Z-score. Similar results were obtained when NAFLD (instead of NASH) was included in the model. WB BMD Z-scores were significantly and independently associated with NASH (standardized β coefficient, -0.248;P < 0.05) and fat mass (standardized β coefficient, -0.224;P < 0.05). CONCLUSION: This study reveals that NAFLD is associated with low BMD in obese children, and that systemic, low-grade inflammation may accelerate loss of bone mass in patients with NAFLD.
文摘Development of type 2 diabetes has been linked to β-cell failure coupled with insulin resistance and obesity. Adipose tissue, known as the fat store, secretes a number of hormones and proteins collectively termed adipokines some of which regulate insulin sensitivity. Dysregulation in the secretion of adipokines has been linked to insulin resistance and type 2 diabetes. In this review, we sum-marized evidence of the role of adipokines with focus on leptin, adiponectin, adipsin, visfatin and apelin in the pathogenesis of type 2 diabetes and discussed the potential of saponins to modify the ill-regulated adipokines secretions, which could promote the use of this class of phytochemicals as potential antidiabetics agents.
文摘Atherosclerotic cardiovascular disease is a major health problem around the world.Obesity is a primary risk factor for atherosclerosis and is associated with increased morbidity and mortality of cardiovascular diseases.However,the precise molecular pathways underlying this close association remain poorly understood.Adipokines are cytokines,chemokines and hormones secreted by adipose tissue that couple the regulation of lipid accumulation,inflammation,and atherogenesis,and therefore serve to link obesity with cardiovascular disorders.Obesity-related disorders including metabolic syndrome,diabetes,atherosclerosis,hypertension,and coronary artery disease are associated with dysregulated adipokine(s) expression.Recent studies demonstrate the proinflammatory effects as well as atherogenic properties of adipokines.Adipokines also participate in the regulation of endothelial function,which is an early event in atherosclerosis.By contrast,adiponectin,an adipocyte-derived hormone,exerts anti-inflammatory,anti-atherogenic and vascular protective effects.Furthermore,there is an interactive association among adipokines,by which adipokines reciprocally regulate each other’s expression.Understanding this interplay may reveal plausible mechanisms for treating atherosclerosis and coronary heart disease by modulating adipokine(s) expression.In this review,we discuss insights into the role and the therapeutic potential of adipokines as mediators of atherosclerosis.
文摘Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding ofthe mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.
文摘BACKGROUNDGhrelin is an adipokine that plays an important role in energy balance. Expressionof ghrelin and ghrelin receptor has been investigated in different tissues andtumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectaltumors are scarce and no data on expression of ghrelin and its receptor incolorectal adenomas has been published. Ghrelin and ghrelin receptor werehighly expressed in colon carcinoma cells while expression was decreased in lessdifferentiated tumors, presuming that ghrelin might be important in early phasesof tumorigenesis.AIMTo investigate the expression of ghrelin and ghrelin receptor in human colorectaladenomas and adjacent colorectal tissue.METHODSIn this prospective study (conducted from June 2015 until May 2019) we included92 patients (64 male and 28 female) who underwent polypectomy for colorectaladenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. After endoscopicremoval of colorectal adenoma, an additional sample of colon mucosa in theproximity of the adenoma was collected for pathohistological analysis. Adenomaswere graded according to the stage of dysplasia, and ghrelin and ghrelin receptorexpression were determined immunohistochemically in both adenoma andadjacent colon tissue using the polyclonal antibody for ghrelin (ab150514,ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAMInc, Cambridge, United States). Categorical and nominal variables were describedthrough frequencies and proportions and the difference between specific groupswere analyzed with Fisher’s and Fisher-Freeman-Halton’s method respectively.Spearman's rank correlation coefficient was determined for correlation ofexpression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissuewith the grade of adenoma dysplasia.RESULTSAmong 92 patients with colorectal adenoma 43 had adenomas with high-gradedysplasia (46.7%). High expression of ghrelin was 7 times more common in highgradeadenoma compared to low-grade adenomas (13.95% to 2.04%, P = 0.048),while the expression of ghrelin in adjacent colon tissue was low. We found nocorrelation between ghrelin receptor expression in adenoma and adjacent colontissue and the grade of colorectal adenoma dysplasia. The most significantcorrelation was found between ghrelin and ghrelin receptor expression inadenomas with high-grade dysplasia (rho = 0.519, P < 0.001).CONCLUSIONGhrelin and ghrelin receptor are expressed in colorectal adenoma and adjacenttissue with ghrelin expression being more pronounced in high grade dysplasia asa possible consequence of increased local synthesis.
文摘Aim Adipose tissue releases adipokines that play important roles in metabolic and cardiocerebro- vascu- lar homeostasis. This study was to discover novel adipokines using caloric restriction model. Methods Adipokine candidates were captured by gene array and bioinformatics analysis and verified by preparation of recombinant pro- tein and antibody. Results We established a potential secreted protein database containing 208 genes and identi- fied a novel adipokine, Subfatin, that was the highest expressed in subcutaneous fat of both rodents and humans a- mong 15 detected tissues. The secreted mammalian Subfatin was a glycosylated protein. Subfatin was located dif- fusely throughout the adipose tissue except lipid droplets, with comparable expression between adipocytes and stro- real cells, but much lower expression in macrophages than adipocytes. Subfatin was downregulated in white adipose tissue of caloric restriction rats, whereas dramatically upregulated during white adipocyte differentiation as well as in white adipose tissue of diet-induced obese mice. Subfatin was annotated as Meteorin-like （Metrnl） in public data- bases, a similar transcript of Meteorin （Metrn, also known as glial cell differentiation regulator）. Meteorin dis- played a brain-specific expression and was scarce in various adipose tissues, in contrast to the tissue expression pat- terns of Subfatin. Conclusions Subfatin is a novel adipokine regulated by adipogenesis and obesity, with tissue distribution different from its homologue Meteorin.
文摘Growth rate affects adipose tissue development and variations in growth rate may potentially impact adipokine expression. Samples of subcutaneous (SQ) and perirenal (PR) adipose tissues and longissimus muscle were collected at day 21 of age from the fastest and slowest growing piglets within seven litters. Reverse transcription and real-time PCR were used to quantify adipokine mRNA abundance. Leptin, adiponectin, tumor necrosis factor α (TNFα ) and lipoprotein lipase (LPL) mRNA abundance were lower in SQ from slow growing piglets (SGP) than in fast growing piglets (FGP, P α gene expression were reduced in PR from SGP in comparison to FGP (P β (IL1β), IL15 and LPL were increased in the longissimus of SGP relative to FGP (P < 0.05). Analysis of mRNA abundance for these adipokines within adipose tissue at day 21 of age demonstrated that the effect of growth rate on adipokine expression varies among different adipokines and the internal and external sites of adipose tissue deposition (PR versus SQ). The increase in longissimus expression of LPL and IL15 suggests that nutrient partitioning for energy use may be greater in the skeletal muscle of the SGP.
