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
AIM: To examine the association between obesity-related adipokines (adiponectin, leptin, resistin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and colorectal cancer (CRC) risk.
AIM: To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2 cells.
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 analyze the prognostic value of adipokines in predicting the course,complications and fatal outcome of acute pancreatitis(AP).METHODS:We performed the search of PubMed database and the systemic analysis of the ...AIM:To analyze the prognostic value of adipokines in predicting the course,complications and fatal outcome of acute pancreatitis(AP).METHODS:We performed the search of PubMed database and the systemic analysis of the literature for both experimental and human studies on prognostic value of adipokines in AP for period 2002-2012.Only the papers that described the use of adipokines for prediction of severity and/or complications of AP were selected for further analysis.Each article had to contain information about the levels of measured adipokines,diagnosis and verification of AP,to specify presence of pancreatic necrosis,organ dysfunction and/or mortality rates.From the very beginning,study was carried out adhering to the PRISMA checklist and flowchart for systemic reviews.To assess quality of all included human studies,the Quality Assessment of Diagnostic Accuracy Studies tool was used.Because of the high heterogeneity between the studies,it was decided to refrain from the statistical processing or meta-analysis of the available data.RESULTS:Nine human and three experimental studies were included into review.In experimental studies significant differences between leptin concentrations at 24 and 48 h in control,acute edematous and acute necrotizing pancreatitis groups were found(P = 0.027 and P < 0.001).In human studies significant differences between leptin and resitin concentrations in control and acute pancreatitis groups were found.1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AP.This threshold yielded a sensitivity of 70%,specificity 85%,positive predictive value 64%,negative predictive value88%(area under curve 0.75).Resistin and visfatin concentrations differ significantly between mild and severe acute pancreatitis groups,they correlate with severity of disease,need for interventions and outcome.Both adipokines are good markers for parapancreatic necrosis and the cut-off values of 11.9 ng/mL and 1.8 ng/mL respectively predict the high ranges of radiological scores.However,the review revealed that all nine human studies with adipokines are very different in terms of methodology and objectives,so it is difficult to generalize their results.It seems that concentrations of the leptin and resistin increases significantly in patients with acute pancreatitis compared with controls.Serum levels of adiponectin,visfatin and especially resitin(positive correlation with Acute Physiology and Chronic Health Evaluation Ⅱ,Ranson and C-reactive protein) are significantly different in mild acute pancreatitis and severe acute pancreatitis patients,so,they can serve as a markers for the disease severity prediction.Resistin and visfatin can also be used for pancreatic and parapancreatic necrosis prediction,interventions needs and possible,outcome.CONCLUSION:High levels of adipokines could allow for prediction of a severe disease course and outcome even in small pancreatic lesions on computed tomography scans.展开更多
Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of N...Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.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
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 non-alcoholic 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
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
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 l...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.展开更多
The association between adipokines and inflammatory periodontal diseases has been studied over the last two decades. This review was intended to explore the observation that periodontal therapy may lead to an improvem...The association between adipokines and inflammatory periodontal diseases has been studied over the last two decades. This review was intended to explore the observation that periodontal therapy may lead to an improvement of adipokines in diabetic patients. In summary, substantial evidence suggests that diabetes is associated with increased prevalence, extent and severity of periodontitis. Numerous mechanisms have been elucidated to explain the impact of diabetes on the periodontium. However, current knowledge concerning the role of major adipokines indicates only some of their associations with the pathogenesis of periodontitis in type 2 diabetes. Conversely, treatment of periodontal disease and reduction of oral inflammation may have positive effects on the diabetic condition, although evidence for this remains somewhat equivocal.展开更多
Objective To explore the role of adipokines including insulin, resistin, leptin, adiponectin, acylation stimulating protein （ASP） and complement C3 （C3） in various types of obesity （peripheral obesity, abdominal ...Objective To explore the role of adipokines including insulin, resistin, leptin, adiponectin, acylation stimulating protein （ASP） and complement C3 （C3） in various types of obesity （peripheral obesity, abdominal obesity and mixed obesity） in Chinese children and adolescents, and their relationships with body size and pubertal development. Methods Children and adolescents （n=3 508） aged 6 to 18 years, with 1 788 boys and 1 720 girls were assessed for body mass index, waist circumference, pubertal development, blood insulin, resistin, leptin, adiponectin, ASP and C3 levels. Three types of obesity [peripheral obesity （n=43）, abdominal obesity （n=473）, mixed obesity （n=1 187）] and non‐obese control （n=1 805） were defined with combined use of Chinese body mass index and waist circumference criteria. Results Serum resistin, leptin and adiponectin levels were higher in girls than those in boys （all P0.01）. Insulin and leptin increased and adiponectin decreased across five Tanner stages in both girls and boys （all P0.001）, while ASP changed only in girls （P0.001） and C3 only in boys （P0.001）. Insulin, leptin and ASP were higher, but adiponectin was lower in all three types of obesity vs. the non‐obese control （all P0.05）. The greatest abnormalities of all six adipokines were found in the mixed obesity group. With inclusion of body mass index and waist circumference in simultaneous regression analyses, both body size indices were independently and significantly correlated with insulin, leptin and adiponectin after age and gender adjustment. Compared with waist circumference, the body mass index was stronger in interpreting insulin, leptin, adiponectin and ASP levels, whereas it was weaker in explaining variance of plasma C3. Conclusions Obese children have a worse metabolic profile with high insulin, resistin, leptin, ASP and C3, and low adiponectin levels. The adipokine profile in mixed obesity is worse than that in peripheral or abdominal obesity. Identification of obese subjects with a malignant adipokine profile using a combination of body mass index and waist circumference is important for the prevention of obesity‐related disease.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
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.
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 obesity-related adipokines (adiponectin, leptin, resistin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and colorectal cancer (CRC) risk.
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 HepG2 cells.
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 analyze the prognostic value of adipokines in predicting the course,complications and fatal outcome of acute pancreatitis(AP).METHODS:We performed the search of PubMed database and the systemic analysis of the literature for both experimental and human studies on prognostic value of adipokines in AP for period 2002-2012.Only the papers that described the use of adipokines for prediction of severity and/or complications of AP were selected for further analysis.Each article had to contain information about the levels of measured adipokines,diagnosis and verification of AP,to specify presence of pancreatic necrosis,organ dysfunction and/or mortality rates.From the very beginning,study was carried out adhering to the PRISMA checklist and flowchart for systemic reviews.To assess quality of all included human studies,the Quality Assessment of Diagnostic Accuracy Studies tool was used.Because of the high heterogeneity between the studies,it was decided to refrain from the statistical processing or meta-analysis of the available data.RESULTS:Nine human and three experimental studies were included into review.In experimental studies significant differences between leptin concentrations at 24 and 48 h in control,acute edematous and acute necrotizing pancreatitis groups were found(P = 0.027 and P < 0.001).In human studies significant differences between leptin and resitin concentrations in control and acute pancreatitis groups were found.1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AP.This threshold yielded a sensitivity of 70%,specificity 85%,positive predictive value 64%,negative predictive value88%(area under curve 0.75).Resistin and visfatin concentrations differ significantly between mild and severe acute pancreatitis groups,they correlate with severity of disease,need for interventions and outcome.Both adipokines are good markers for parapancreatic necrosis and the cut-off values of 11.9 ng/mL and 1.8 ng/mL respectively predict the high ranges of radiological scores.However,the review revealed that all nine human studies with adipokines are very different in terms of methodology and objectives,so it is difficult to generalize their results.It seems that concentrations of the leptin and resistin increases significantly in patients with acute pancreatitis compared with controls.Serum levels of adiponectin,visfatin and especially resitin(positive correlation with Acute Physiology and Chronic Health Evaluation Ⅱ,Ranson and C-reactive protein) are significantly different in mild acute pancreatitis and severe acute pancreatitis patients,so,they can serve as a markers for the disease severity prediction.Resistin and visfatin can also be used for pancreatic and parapancreatic necrosis prediction,interventions needs and possible,outcome.CONCLUSION:High levels of adipokines could allow for prediction of a severe disease course and outcome even in small pancreatic lesions on computed tomography scans.
文摘Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.
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 non-alcoholic 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 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 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.
文摘The association between adipokines and inflammatory periodontal diseases has been studied over the last two decades. This review was intended to explore the observation that periodontal therapy may lead to an improvement of adipokines in diabetic patients. In summary, substantial evidence suggests that diabetes is associated with increased prevalence, extent and severity of periodontitis. Numerous mechanisms have been elucidated to explain the impact of diabetes on the periodontium. However, current knowledge concerning the role of major adipokines indicates only some of their associations with the pathogenesis of periodontitis in type 2 diabetes. Conversely, treatment of periodontal disease and reduction of oral inflammation may have positive effects on the diabetic condition, although evidence for this remains somewhat equivocal.
基金supported by the grants to JM from the National Natural Science Foundation of China (30872165)the Beijing Key Science and Technology Program (D08050700320801) from the Beijing Municipal Science and Technology Commission+2 种基金the Beijing Health System Leading Scientist Program (2009‐1‐08) from the Beijing Health Bureauby a grant from the Canadian Institutes of Health Research to KC (#77532)FRSQ‐NSFC Québec‐China exchange program (KC),and KC holds a Canada Research Chair in Adipose Tissue
文摘Objective To explore the role of adipokines including insulin, resistin, leptin, adiponectin, acylation stimulating protein （ASP） and complement C3 （C3） in various types of obesity （peripheral obesity, abdominal obesity and mixed obesity） in Chinese children and adolescents, and their relationships with body size and pubertal development. Methods Children and adolescents （n=3 508） aged 6 to 18 years, with 1 788 boys and 1 720 girls were assessed for body mass index, waist circumference, pubertal development, blood insulin, resistin, leptin, adiponectin, ASP and C3 levels. Three types of obesity [peripheral obesity （n=43）, abdominal obesity （n=473）, mixed obesity （n=1 187）] and non‐obese control （n=1 805） were defined with combined use of Chinese body mass index and waist circumference criteria. Results Serum resistin, leptin and adiponectin levels were higher in girls than those in boys （all P0.01）. Insulin and leptin increased and adiponectin decreased across five Tanner stages in both girls and boys （all P0.001）, while ASP changed only in girls （P0.001） and C3 only in boys （P0.001）. Insulin, leptin and ASP were higher, but adiponectin was lower in all three types of obesity vs. the non‐obese control （all P0.05）. The greatest abnormalities of all six adipokines were found in the mixed obesity group. With inclusion of body mass index and waist circumference in simultaneous regression analyses, both body size indices were independently and significantly correlated with insulin, leptin and adiponectin after age and gender adjustment. Compared with waist circumference, the body mass index was stronger in interpreting insulin, leptin, adiponectin and ASP levels, whereas it was weaker in explaining variance of plasma C3. Conclusions Obese children have a worse metabolic profile with high insulin, resistin, leptin, ASP and C3, and low adiponectin levels. The adipokine profile in mixed obesity is worse than that in peripheral or abdominal obesity. Identification of obese subjects with a malignant adipokine profile using a combination of body mass index and waist circumference is important for the prevention of obesity‐related disease.
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.
