Our prior investigations have established that Inonotus obliquus(Chaga)possesses hypoglycemic effects.Persistent hyperglycemia is known to precipitate renal function abnormalities.The functionality of the kidneys is i...Our prior investigations have established that Inonotus obliquus(Chaga)possesses hypoglycemic effects.Persistent hyperglycemia is known to precipitate renal function abnormalities.The functionality of the kidneys is intricately linked to the levels of cyclic guanosine-3',5'-monophosphate(cGMP),which are influenced by the activities of nitric oxide synthase(NOS)and phosphodiesterase(PDE).Enhanced cGMP levels can be achieved either through the upregulation of NOS activity or the downregulation of PDE activity.The objective of the current study is to elucidate the effects of Chaga on disorders of glucolipid metabolism and renal abnormalities in rats with type 2 diabetes mellitus(T2DM),while concurrently examining the NOS-cGMP-PDE5 signaling pathway.A model of T2DM was developed in rats using a high-fat diet(HFD)combined with streptozotocin(STZ)administration,followed by treatment with Chaga extracts at doses of 50 and 100 mg·kg^(−1)for eight weeks.The findings revealed that Chaga not only mitigated metabolic dysfunctions,evidenced by improvements in fasting blood glucose,total cholesterol,triglycerides,and insulin resistance,but also ameliorated renal function markers,including serum creatinine,urine creatinine(UCr),blood urea nitrogen,24-h urinary protein,and estimated creatinine clearance.Additionally,enhancements in glomerular volume,GBM thickness,podocyte foot process width(FPW),and the mRNA and protein expressions of podocyte markers,such as nephrin and wilms tumor-1,were observed.Chaga was found to elevate cGMP levels in both serum and kidney tissues by increasing mRNA and protein expressions of renal endothelial NOS and neural NOS,while simultaneously reducing the expressions of renal inducible NOS and PDE5.In summary,Chaga counteracts HFD/STZ-induced glucolipid metabolism and renal function disturbances by modulating the NOS-cGMP-PDE5 signaling pathway.This research supports the potential application of Chaga in the clinical prevention and treatment of T2DM and diabetic nephropathy(DN),with cGMP serving as a potential therapeutic target.展开更多
It has been widely accepted that resistant starch(RS)provides numerous health benefits for human.In this research,we aimed at evaluating the performance of novel starch-lipid complexes,RS5,in comparison with RS2 on ph...It has been widely accepted that resistant starch(RS)provides numerous health benefits for human.In this research,we aimed at evaluating the performance of novel starch-lipid complexes,RS5,in comparison with RS2 on physical features,glucolipids metabolism,inflammation,and gut microbiota profiles of type 2 diabetes mellitus(T2DM)rats.The T2DM model was established by streptozotocin injection to the high-fat-sugar fed rats.According to a serial of biochemical analyses,we found that RS5 diets were strongly correlated with enhanced homeostatic model assessment for insulin secretion(HOMA-IS),high-density lipoprotein cholesterol(HDL-C),adiponectin(ADP),insulin action index(IAI),glucagon-like peptide-1(GLP1),and short-chain fatty acids(SCFAs)in T2DM rats whilst negatively associated with the low-density lipoprotein(LDL-C)and inflammatory cytokines,showing the capabilities to ameliorate T2DM symptoms by regulation of glucolipid metabolism,gut metabolites,and inflammation.On the other hand,RS2-enriched supplementations were influential in the mediation of insulin secretion to improve glucose metabolism.The increasing evidence collected herein suggested that intestinal microbiota could mediate glucolipids metabolism and alleviate inflammation after certain microflora nourished by RS.In addition,RS intake made an impact on phosphoinositide 3-kinase/protein kinase B signaling pathway that might contribute to the improvement of glucose metabolism,insulin resistance,and inflammatory responses.展开更多
Cell wall is a basic component of bacteria that promotes bacteria to adapt the complicated environment as well as play an essential role in antimicrobial resistance.The structure of bacterial cell wall is remarkably r...Cell wall is a basic component of bacteria that promotes bacteria to adapt the complicated environment as well as play an essential role in antimicrobial resistance.The structure of bacterial cell wall is remarkably rich,and some complex components,such as peptidoglycan,lipopolysaccharide,and peptidoglycan-arabinogalactan et al.,can only be found in bacteria.Furthermore,the biosynthesis and transfer of these glycolipids are indispensable for bacteria during cell elongation.And the process of biosynthesis and transfer are generally associated with metabolism and sophisticated enzyme mechanisms.However,how the metabolic process takes place,what role enzymes play in this process and how they function have been major concerns for scientists in this field.Numerous significant progresses on fluorescent probes and biological imaging bring opportunity for the studying of metabolism and enzyme mechanisms recently due to its non-invasive and high sensitivity.In this review,we focused on metabolic fluorescent probes for the detection of glycolipids in bacterial cell wall and highlighted the involving mechanisms and biological application.展开更多
Lipids and glucose exert many essential physiological functions,such as providing raw materials or energy for cellular biosynthesis,regulating cell signal transduction,and maintaining a constant body temperature.Dysre...Lipids and glucose exert many essential physiological functions,such as providing raw materials or energy for cellular biosynthesis,regulating cell signal transduction,and maintaining a constant body temperature.Dysregulation of lipid and glucose metabolism can lead to glucolipid metabolic disorders linked to various metabolic diseases,such as obesity,diabetes,and cardiovascular disease.Therefore,intervention in glucolipid metabolism is a key therapeutic strategy for the treatment of metabolic diseases.Activating transcription factor 3(ATF3)is a transcription factor that acts as a hub of the cellular adaptive-response network and plays a pivotal role in the regulation of inflammation,apoptosis,DNA repair,and oncogenesis.Emerging evidence has illustrated the vital roles of ATF3 in glucolipid metabolism.ATF3 inhibits intestinal lipid absorption,enhances hepatic triglyceride hydrolysis and fatty acid oxidation,promotes macrophage reverse cholesterol transport,and attenuates the progression of western diet-induced nonalcoholic fatty liver disease and atherosclerosis.In addition to its role in lipid metabolism,ATF3 has also been identified as an important regulator of glucose metabolism.Here,we summarize the recent advances in the understanding of ATF3,mainly focusing on its role in glucose and lipid metabolism and potential therapeutic implications.展开更多
Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metaboli...Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled by a modification of bile acid derivatives concentra-tions in the colonic content.The plausible links between these modified parameters are discussed.展开更多
Objective To explore the relationship between serum osteocalcin levels and glucolipid metabolism in elderly type 2 diabetic patients with non-alcoholic fatty liver disease(NAFLD).Methods Data collected from 97 pa-tien...Objective To explore the relationship between serum osteocalcin levels and glucolipid metabolism in elderly type 2 diabetic patients with non-alcoholic fatty liver disease(NAFLD).Methods Data collected from 97 pa-tients with type 2 diabetes mellitus(T2DM)admitted to the Department of Geriatric Endocrinology of the First Affiliated hospital of Zhengzhou University from June展开更多
Objective:To investigate the correlation between serum secretory frizzled-related protein 5(SFRP-5)expression levels and insulin resistance and glucolipid metabolism in patients with gestational diabetes mellitus(GDM)...Objective:To investigate the correlation between serum secretory frizzled-related protein 5(SFRP-5)expression levels and insulin resistance and glucolipid metabolism in patients with gestational diabetes mellitus(GDM).Methods:Baseline data were collected from 58 patients with GDM and 51 healthy controls who were admitted Affiliated Hospital of Hebei University from May 2020 to June 2022.sSTRA5 concentrations in peripheral blood of pregnant women were measured,and SFRP-5 levels in patients with different GDM types and normal controls were analyzed by logistic regression models.Results:The levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),fasting blood glucose(FBG),fasting insulin(FINS),hemoglobin A1c(HbA1c),and homeostasis model assessment-estimated insulin resistance(HOMA-IR)were higher in the observation group than in the control group,with statistically significant differences(P<0.05),while the expression levels of high-density lipoprotein cholesterol(HDL-C)and serum SFRP-5 were lower than in the control group,with statistically significant differences(P<0.05);serum SFRP-5,TG,TC,FBG,and HOMA-IR were all risk factors for GDM(P<0.05).Conclusion:Elevated serum sSTRA5 may be involved in the regulation of insulin resistance in the body and the regulation of blood glucose in the body by affecting lipid metabolism and inflammatory response.展开更多
Background Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy met...Background Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase(AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation.Results Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver;dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation.Conclusions Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we high-light the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.展开更多
Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ...Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.展开更多
Glucolipid metabolic disease （GLMD）, a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metaboli...Glucolipid metabolic disease （GLMD）, a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively. This review article aims to summarize the current advances in the investigation of the functional roles and the underling mechanisms of the interplay between the liver and adipose tissue in the modulation of GLMD development. Fibroblast growth factor 21 （FGF21） and adiponectin represent the two major hormones secreted from the liver and adipose tissues, respectively. FGF21 exerts pleiotropic effects on regulating glucose and lipid homeostasis majorly through inducing the expression and secretion of adiponectin. Therefore, FGF21-adiponectin axis functions as the key mediator for the crosstalk between the liver and adipose tissue to exert the beneficial effects on the maintenance of the homeostasis of energy consumption. The liver- and adipose tissue-derived factors with pleiotropic effects on regulating of lipid and glucose metabolism function as the key mediator for the crosstalk between these two highly active metabolic organs, thereby coordinating the initiation and development of GLMD.展开更多
Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settin...Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattem of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine （WM）. On the basis of the combination of the advantages of integrated Chinese medicine （CM） and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease （GLMD） is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system,insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as ＂Gan （Liver） Shi Shu Xie＂ （dysfunction of Gan in metabolism and emotion regulation） that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of ＂Liver-based regulatory system for metabolic homeostasis＂ to be introduced further. The comprehensive prevention and control strategy ＂Tiao Gan Qi Shu Hua Zhuo＂ （modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness）. Its representative formula Fufang Zhenzhu Tiaozhi Capsule （复方贞术调脂胶囊） is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carded out to further interpret and explain of the scientific connotation of GLMD.展开更多
Antibiotics have been identified as obesogens contributing to the prevalence of obesity.Moreover,their environmental toxicity shows sex dependence,which might also explain the sex-dependent obesity observed.Yet,the di...Antibiotics have been identified as obesogens contributing to the prevalence of obesity.Moreover,their environmental toxicity shows sex dependence,which might also explain the sex-dependent obesity observed.Yet,the direct evidence for such a connection and the underlying mechanisms remain to be explored.In this study,the effects of tetracycline,which is a representative antibiotic found in both environmental and food samples,on Drosophila melanogaster were studied with consideration of both sex and circadian rhythms(represented by the eclosion rhythm).Results showed that in morning-eclosed adults,tetracycline significantly stimulated the body weight of females(AM females)at 0.1,1.0,10.0 and 100.0μg/L,while tetracycline only stimulated the body weight of males(AM males)at 1.0μg/L.In the afternoon-eclosed adults,tetracycline significantly stimulated the body weight of females(PM females)at 0.1,1.0 and 100.0μg/L,while it showed more significant stimulation in males(PM males)at all concentrations.Notably,the stimulation levels were the greatest in PMmales among all the adults.The results showed the clear sex dependence of the obesogenic effects,which was diminished by dysrhythmia.Further biochemical assays and clustering analysis suggested that the sex-and rhythm-dependent obesogenic effects resulted from the bias toward lipogenesis against lipolysis.Moreover,theywere closely related to the preference for the energy storage forms of lactate and glucose and also to the presence of excessive insulin,with the involvement of glucolipid metabolism.Such relationships indicated potential bridges between the obesogenic effects of pollutants and other diseases,e.g.,cancer and diabetes.展开更多
基金supported by the Medical Key Research Projects of Shanxi Province(No.2020XM02)the Local Science and Technology Development Funds Projects Guided by Central Government(No.YDZJSX2021C027)+2 种基金the Basic Research Program of Shanxi Province(No.202103021224370)the Key R&D Project of Shanxi Province[International Scientific and Technological Cooperation,Independent Topics,(No.201903D421061)]Wu Jieping Medical Foundation(No.320.6750.2021-08-10).
文摘Our prior investigations have established that Inonotus obliquus(Chaga)possesses hypoglycemic effects.Persistent hyperglycemia is known to precipitate renal function abnormalities.The functionality of the kidneys is intricately linked to the levels of cyclic guanosine-3',5'-monophosphate(cGMP),which are influenced by the activities of nitric oxide synthase(NOS)and phosphodiesterase(PDE).Enhanced cGMP levels can be achieved either through the upregulation of NOS activity or the downregulation of PDE activity.The objective of the current study is to elucidate the effects of Chaga on disorders of glucolipid metabolism and renal abnormalities in rats with type 2 diabetes mellitus(T2DM),while concurrently examining the NOS-cGMP-PDE5 signaling pathway.A model of T2DM was developed in rats using a high-fat diet(HFD)combined with streptozotocin(STZ)administration,followed by treatment with Chaga extracts at doses of 50 and 100 mg·kg^(−1)for eight weeks.The findings revealed that Chaga not only mitigated metabolic dysfunctions,evidenced by improvements in fasting blood glucose,total cholesterol,triglycerides,and insulin resistance,but also ameliorated renal function markers,including serum creatinine,urine creatinine(UCr),blood urea nitrogen,24-h urinary protein,and estimated creatinine clearance.Additionally,enhancements in glomerular volume,GBM thickness,podocyte foot process width(FPW),and the mRNA and protein expressions of podocyte markers,such as nephrin and wilms tumor-1,were observed.Chaga was found to elevate cGMP levels in both serum and kidney tissues by increasing mRNA and protein expressions of renal endothelial NOS and neural NOS,while simultaneously reducing the expressions of renal inducible NOS and PDE5.In summary,Chaga counteracts HFD/STZ-induced glucolipid metabolism and renal function disturbances by modulating the NOS-cGMP-PDE5 signaling pathway.This research supports the potential application of Chaga in the clinical prevention and treatment of T2DM and diabetic nephropathy(DN),with cGMP serving as a potential therapeutic target.
基金the National Natural Science Foundation of China(3203000230)the Fundamental Research Funds for the Central Universities,Nankai University(63231172)the Natural Science Foundation of Henan(222300420158),for supporting this research.
文摘It has been widely accepted that resistant starch(RS)provides numerous health benefits for human.In this research,we aimed at evaluating the performance of novel starch-lipid complexes,RS5,in comparison with RS2 on physical features,glucolipids metabolism,inflammation,and gut microbiota profiles of type 2 diabetes mellitus(T2DM)rats.The T2DM model was established by streptozotocin injection to the high-fat-sugar fed rats.According to a serial of biochemical analyses,we found that RS5 diets were strongly correlated with enhanced homeostatic model assessment for insulin secretion(HOMA-IS),high-density lipoprotein cholesterol(HDL-C),adiponectin(ADP),insulin action index(IAI),glucagon-like peptide-1(GLP1),and short-chain fatty acids(SCFAs)in T2DM rats whilst negatively associated with the low-density lipoprotein(LDL-C)and inflammatory cytokines,showing the capabilities to ameliorate T2DM symptoms by regulation of glucolipid metabolism,gut metabolites,and inflammation.On the other hand,RS2-enriched supplementations were influential in the mediation of insulin secretion to improve glucose metabolism.The increasing evidence collected herein suggested that intestinal microbiota could mediate glucolipids metabolism and alleviate inflammation after certain microflora nourished by RS.In addition,RS intake made an impact on phosphoinositide 3-kinase/protein kinase B signaling pathway that might contribute to the improvement of glucose metabolism,insulin resistance,and inflammatory responses.
基金financial support from the National Natural Science Foundation of China(21676113,21772054)the 111 Project B17019,Scholar Support Program of CCNU(0900–31101090002)+4 种基金Excellent Doctorial Dissertation Cultivation Grant of CCNU from the colleges’basic research and operation of MOE(2019YBZZ029)funded by the Research Fund Program of Guangdong Key Laboratory of Radioactive and Rare Resource Utilization(2018B030322009)supported by Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules(KLSAOFM2012)Hubei University,Wuhan 430062,P.R.China,Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica(No.BCMM202101)supported by State Key Laboratory of Chemical Oncogenomics(Shenzhen)
文摘Cell wall is a basic component of bacteria that promotes bacteria to adapt the complicated environment as well as play an essential role in antimicrobial resistance.The structure of bacterial cell wall is remarkably rich,and some complex components,such as peptidoglycan,lipopolysaccharide,and peptidoglycan-arabinogalactan et al.,can only be found in bacteria.Furthermore,the biosynthesis and transfer of these glycolipids are indispensable for bacteria during cell elongation.And the process of biosynthesis and transfer are generally associated with metabolism and sophisticated enzyme mechanisms.However,how the metabolic process takes place,what role enzymes play in this process and how they function have been major concerns for scientists in this field.Numerous significant progresses on fluorescent probes and biological imaging bring opportunity for the studying of metabolism and enzyme mechanisms recently due to its non-invasive and high sensitivity.In this review,we focused on metabolic fluorescent probes for the detection of glycolipids in bacterial cell wall and highlighted the involving mechanisms and biological application.
基金the National Natural Science Foundation of China(32271218 to Y.X.)in part by grants from the National Natural Science Foundation of China(81670519 to J.L.)the Science and Technology Commission of Shanghai Municipality(22ZR1414300 to H.W.).
文摘Lipids and glucose exert many essential physiological functions,such as providing raw materials or energy for cellular biosynthesis,regulating cell signal transduction,and maintaining a constant body temperature.Dysregulation of lipid and glucose metabolism can lead to glucolipid metabolic disorders linked to various metabolic diseases,such as obesity,diabetes,and cardiovascular disease.Therefore,intervention in glucolipid metabolism is a key therapeutic strategy for the treatment of metabolic diseases.Activating transcription factor 3(ATF3)is a transcription factor that acts as a hub of the cellular adaptive-response network and plays a pivotal role in the regulation of inflammation,apoptosis,DNA repair,and oncogenesis.Emerging evidence has illustrated the vital roles of ATF3 in glucolipid metabolism.ATF3 inhibits intestinal lipid absorption,enhances hepatic triglyceride hydrolysis and fatty acid oxidation,promotes macrophage reverse cholesterol transport,and attenuates the progression of western diet-induced nonalcoholic fatty liver disease and atherosclerosis.In addition to its role in lipid metabolism,ATF3 has also been identified as an important regulator of glucose metabolism.Here,we summarize the recent advances in the understanding of ATF3,mainly focusing on its role in glucose and lipid metabolism and potential therapeutic implications.
基金supported by the National Natural Science Foundation of China(U20A2056)Special Funds for Construction of Innovative Provinces in Hunan Province(2019RS3022).
文摘Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled by a modification of bile acid derivatives concentra-tions in the colonic content.The plausible links between these modified parameters are discussed.
文摘Objective To explore the relationship between serum osteocalcin levels and glucolipid metabolism in elderly type 2 diabetic patients with non-alcoholic fatty liver disease(NAFLD).Methods Data collected from 97 pa-tients with type 2 diabetes mellitus(T2DM)admitted to the Department of Geriatric Endocrinology of the First Affiliated hospital of Zhengzhou University from June
基金Youth Science and Technology Fund of Affiliated Hospital of Hebei University(Project number:2017Q024)Baoding City Science and Technology Plan Projects(Project number:2041ZF295)Hebei University Medical Subject Cultivation Project(Project number:2022B03)。
文摘Objective:To investigate the correlation between serum secretory frizzled-related protein 5(SFRP-5)expression levels and insulin resistance and glucolipid metabolism in patients with gestational diabetes mellitus(GDM).Methods:Baseline data were collected from 58 patients with GDM and 51 healthy controls who were admitted Affiliated Hospital of Hebei University from May 2020 to June 2022.sSTRA5 concentrations in peripheral blood of pregnant women were measured,and SFRP-5 levels in patients with different GDM types and normal controls were analyzed by logistic regression models.Results:The levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),fasting blood glucose(FBG),fasting insulin(FINS),hemoglobin A1c(HbA1c),and homeostasis model assessment-estimated insulin resistance(HOMA-IR)were higher in the observation group than in the control group,with statistically significant differences(P<0.05),while the expression levels of high-density lipoprotein cholesterol(HDL-C)and serum SFRP-5 were lower than in the control group,with statistically significant differences(P<0.05);serum SFRP-5,TG,TC,FBG,and HOMA-IR were all risk factors for GDM(P<0.05).Conclusion:Elevated serum sSTRA5 may be involved in the regulation of insulin resistance in the body and the regulation of blood glucose in the body by affecting lipid metabolism and inflammatory response.
基金funded by the National Key Research and Development Program of China (2021YFD1300403)。
文摘Background Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase(AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation.Results Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver;dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation.Conclusions Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we high-light the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.
文摘Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.
文摘Glucolipid metabolic disease （GLMD）, a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively. This review article aims to summarize the current advances in the investigation of the functional roles and the underling mechanisms of the interplay between the liver and adipose tissue in the modulation of GLMD development. Fibroblast growth factor 21 （FGF21） and adiponectin represent the two major hormones secreted from the liver and adipose tissues, respectively. FGF21 exerts pleiotropic effects on regulating glucose and lipid homeostasis majorly through inducing the expression and secretion of adiponectin. Therefore, FGF21-adiponectin axis functions as the key mediator for the crosstalk between the liver and adipose tissue to exert the beneficial effects on the maintenance of the homeostasis of energy consumption. The liver- and adipose tissue-derived factors with pleiotropic effects on regulating of lipid and glucose metabolism function as the key mediator for the crosstalk between these two highly active metabolic organs, thereby coordinating the initiation and development of GLMD.
基金Supported by the National Natural Science Foundation of China(No.81173626,81530102,and 30973913)
文摘Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattem of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine （WM）. On the basis of the combination of the advantages of integrated Chinese medicine （CM） and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease （GLMD） is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system,insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as ＂Gan （Liver） Shi Shu Xie＂ （dysfunction of Gan in metabolism and emotion regulation） that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of ＂Liver-based regulatory system for metabolic homeostasis＂ to be introduced further. The comprehensive prevention and control strategy ＂Tiao Gan Qi Shu Hua Zhuo＂ （modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness）. Its representative formula Fufang Zhenzhu Tiaozhi Capsule （复方贞术调脂胶囊） is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carded out to further interpret and explain of the scientific connotation of GLMD.
基金supported by the National Natural Science Foundation of China (No. 21976138)the Foundation of State Key Laboratory of Pollution Control and Resource Reuse (Tongji University), China (No. PCRRE20011)the Fundamental Research Funds for the Central Universities (No. 22120180549)
文摘Antibiotics have been identified as obesogens contributing to the prevalence of obesity.Moreover,their environmental toxicity shows sex dependence,which might also explain the sex-dependent obesity observed.Yet,the direct evidence for such a connection and the underlying mechanisms remain to be explored.In this study,the effects of tetracycline,which is a representative antibiotic found in both environmental and food samples,on Drosophila melanogaster were studied with consideration of both sex and circadian rhythms(represented by the eclosion rhythm).Results showed that in morning-eclosed adults,tetracycline significantly stimulated the body weight of females(AM females)at 0.1,1.0,10.0 and 100.0μg/L,while tetracycline only stimulated the body weight of males(AM males)at 1.0μg/L.In the afternoon-eclosed adults,tetracycline significantly stimulated the body weight of females(PM females)at 0.1,1.0 and 100.0μg/L,while it showed more significant stimulation in males(PM males)at all concentrations.Notably,the stimulation levels were the greatest in PMmales among all the adults.The results showed the clear sex dependence of the obesogenic effects,which was diminished by dysrhythmia.Further biochemical assays and clustering analysis suggested that the sex-and rhythm-dependent obesogenic effects resulted from the bias toward lipogenesis against lipolysis.Moreover,theywere closely related to the preference for the energy storage forms of lactate and glucose and also to the presence of excessive insulin,with the involvement of glucolipid metabolism.Such relationships indicated potential bridges between the obesogenic effects of pollutants and other diseases,e.g.,cancer and diabetes.
