Adipokines regulate mesenchymal stem cell osteogenic differentiation

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.

Association between obesity-related adipokines and colorectal cancer:A case-control study and meta-analysis

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.

Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease

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.

Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease

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.

Value of adipokines in predicting the severity of acute pancreatitis:Comprehensive review

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.

Serum adipokines in inflammatory bowel disease

AIM: To investigate serum adipokine levels in inflammatory bowel disease (IBD) patients before treatment and after achieving clinical remission.

Adipokines: Biomarkers for osteoarthritis?

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.

Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis

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.

Effect of periodontal treatment on adipokines in type 2 diabetes

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.

Pharmacological effects of lipid-lowering drugs on circulating adipokines

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.

Adipokines and C-reactive protein in relation to bone mineralization in pediatric nonalcoholic fatty liver disease

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.

Saponins as adipokines modulator: A possible therapeutic intervention for type 2 diabetes

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.

Emerging role of adipokines as mediators in atherosclerosis

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.

Detection of vitamin D in patients with gestational diabetes mellitus and its effects on insulin resistance, adipokines and TNF-α

Objective:To detect vitamin D levels in patients with gestational diabetes mellitus and the influence and clinical effect of Vitamin D supplement on insulin resistance, fatty factors and TNF-α.Methods:A total of 100 patients with GDM from September 2014 to May 2015 in our hospital were selected as object of observation (GDM Group). 52 cases patients with Vitamin D deficiency were randomly divided into two groups. At the same time, 50 cases of healthy pregnant women were selected as normal group. Biochemical indexes of observation group and normal group were detected. Biosynthetic Human Insulin Injection were given to the patients in the control group. The patients in the observation group were supplemented with vitamin D drops on the basis of the treatment of control group. The level of insulin resistance, adipokines and TNF-α were detected in the 2 groups.Results:FBG, PBG, FINS, TG, Visfatin, TNF-α and HOMA-IR in GDM group were higher compared with that in normal group. 25(OH)D3 and APN in GDM group decreased significantly compared with that in normal group. The comparison of TC, HDL-C and LDL-C in the two groups were not statistically significant. PBG, FINS, HOMA-IR, Visfatin and TNF-α in both groups after treatment significantly decreased compared with that before treatment. PBG, Visfatin and TNF-α in treatment group after treatment decreased more significantly than that in control group. FINS, HOMA-IR in treatment group after treatment increased more significantly than that in control group. The decrease of FBG was not obvious and there was no significant difference between the two groups after treatment. APN and 25(OH)D3 in both groups after treatment significantly increased compared with that before treatment. And they in treatment group after treatment increased more significantly than that in control group. In the correlation analysis, 25(OH) D3in serum was positively correlated to the the level of APN. Also, it was negatively correlated to HOMA-IR, Visfatin and TNF-α.Conclusion:Vitamin D levels in patients with gestational diabetes mellitus decreased more significantly compared with that in healthy pregnant women. And the patients with vitamin D deficiency have higher risk to get GDM. Vitamin D can treat GDM by regulating the degree of insulin resistance and the level of adipokines. And it has clinical value in the treatment of GDM.

Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease

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 &#x000b1; 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-&#x003b1; levels were associated independently with steatosis grade of more than 33% [&#x003b2; = 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 &#x0003c; 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [&#x003b2; = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P &#x0003c; 0.05]. Similarly, higher TNF-&#x003b1;, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [&#x003b2; = 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 &#x0003c; 0.05]. Serum IL-8 and TNF-&#x003b1; values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [&#x003b2; = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P &#x0003c; 0.05].CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.

Abnormal Adipokines Associated with Various Types of Obesity in Chinese Children and Adolescents

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.

Adipokines as a novel link between obesity and atherosclerosis

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.

Interplay of adipokines and myokines in cancer pathophysiology: Emerging therapeutic implications

Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding ofthe mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.

Role of adipokines in sarcopenia

Sarcopenia is an age-related disease that mainly involves decreases in muscle mass,muscle strength and muscle function.At the same time,the body fat content increases with aging,especially the visceral fat content.Adipose tissue is an endocrine organ that secretes biologically active factors called adipokines,which act on local and distant tissues.Studies have revealed that some adipokines exert regulatory effects on muscle,such as higher serum leptin levels causing a decrease in muscle function and adiponectin inhibits the transcriptional activity of Forkhead box O3(FoxO3)by activating peroxisome proliferators-activated receptor-γcoactivator-1α(PGC-1α)and sensitizing cells to insulin,thereby repressing atrophy-related genes(atrogin-1 and muscle RING finger 1[MuRF1])to prevent the loss of muscle mass.Here,we describe the effects on muscle of adipokines produced by adipose tissue,such as leptin,adiponectin,resistin,mucin and lipocalin-2,and discuss the importance of these adipokines for understanding the development of sarcopenia.

Bo′s abdominal acupuncture improves disordered metabolism in obese type 2 diabetic rats through regulating fibroblast growth factor 21 and its related adipokines

OBJECTIVE:To investigate the effect of Bo′s abdominal acupuncture(BOAA)on fibroblast growth factor 21(FGF21)and its related adipokines in type 2 diabetes mellitus(T2DM)rats.METHODS:This study established obese T2DM rat model by high-fat diet(HFD)with a dose of streptozotocin(STZ,30 mg/kg).Obese T2DM rats were randomly subdivided into four groups(n=10):negative,BOAA,conventional acupuncture(COA group)and metformin group(Met group)groups.The biochemical parameters,mRNAs,and proteins were analyzed using enzyme-lined immunoassays kits,quantitative polymerase chain reaction and Western blot.RESULTS:Treatment with BOAA attenuated the histopathological changes in visceral fat and restored the alterations in the levels of body weight,fasting blood glucose(FBG),homeostasis model assessment for insulin resistance(HOMA-IR).BOAA treatment significantly decreased the levels of triglyceride,total cholesterol,low density lipoprotein cholesterol,leptin,and increased the serum levels of high-density lipoprotein cholesterol,fibroblast growth factor 21(FGF21),adiponectin(ADP),peroxisome proliferator-activated receptorγ(PPAR-γ),C-peptide(C-P)in obese T2DM rats.Furthermore,BOAA treatment significantly increased the mRNA expressions of FGF21,ADP,leptin,PPAR-γ,PPAR-αand adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPK).Besides,BOAA treatment upregulated the protein expressions of fibroblast growth factor receptors3(FGFR3),PPAR-α,extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),AMPK,p-AMPK,Liver kinase B1(LKB1),phosphorylated LKB1(p-LKB1),acetyl-CoA carboxylase(ACC)and phosphorylated ACC(p-ACC),while downregulated the protein expressions of FGF21 and PPAR-γin visceral fat.CONCLUSIONS:BOAA treatment reduced FBG and body weight,and improved insulin sensitivity through regulating FGF21 signaling pathway and its related adipokine in obese T2DM rats.