OBJECTIVE: To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD). METHODS: After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated. RESULTS: After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1β, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05). CONCLUSION The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.
Adiponectin ; Animals ; Cytokines ; Diet, High-Fat ; Glucose ; Insulin Resistance ; Interleukin-10 ; Liver ; Male ; Minerals ; Non-alcoholic Fatty Liver Disease/pathology* ; Pioglitazone/therapeutic use* ; Rats ; Rats, Wistar ; Resins, Plant ; Resistin/therapeutic use* ; Tumor Necrosis Factor-alpha

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting 30% of the general population and 40% to 70% of obese individuals. Adipose tissue plays a crucial role in its pathogenesis, as it produces and secretes pro- and anti-inflammatory cytokines called adipokines. Adiponectin and leptin have well-determined actions in terms of NAFLD pathophysiology. Adiponectin deficiency is associated with a pro-inflammatory condition, as it is observed in obesity and other metabolic disorders. On the other hand, increased leptin levels, above the normal levels, act as a pro-inflammatory stimulus. Regarding other adipokines (resistin, visfatin, chemerin, retinol-binding protein 4, irisin), data about their contribution to NAFLD pathogenesis and progression are inconclusive. In addition, pharmacological agents like thiazolidinediones (pioglitazone and rosiglitazone), that are used in the management of NAFLD exert favourable effects on adipokine levels, which in turn may contribute to the improvement of liver function. This review summarizes the current knowledge and developments in the association between adipokines and NAFLD and discusses possible therapeutic implications targeting the modulation of adipokine levels as a potential tool for the treatment of NAFLD.
Adipokines* ; Adiponectin ; Adipose Tissue ; Cytokines ; Hand ; Leptin ; Liver ; Liver Diseases ; Nicotinamide Phosphoribosyltransferase ; Non-alcoholic Fatty Liver Disease* ; Obesity ; Resistin ; Thiazolidinediones

PURPOSE: The aim of this study was to investigate the clinical significance of 7 circulating adipokines according to body mass index (BMI) in Korean men with localized prostate cancer (PCa) undergoing radical prostatectomy (RP). MATERIALS AND METHODS: Sixty-two of 65 prospectively enrolled patients with clinically localized PCa who underwent RP between 2015 and 2016 were evaluated. Patients were classified into 2 groups according to their BMI: non-obese (< 25 kg/m²) and obese (≥25 kg/m²). The adipokines evaluated were interleukin-2, insulin-like growth factor 1 (IGF-1), chemerin, C-X-C motif chemokine 10, adiponectin, leptin, and resistin. Multivariate logistic regression analysis was used to identify the independent predictors of advanced tumor stage. RESULTS: We found that obese patients with PCa who underwent RP had a higher incidence of tumors with a high Gleason score (≥8), pathological T3 (pT3) stage, and positive extraprostatic extension than patients with a normal BMI. Additionally, patients with obesity showed significantly lower serum adiponectin and higher serum leptin levels, but did not show differences in other adipokines. Multivariate analysis demonstrated that IGF-1 (odds ratio [OR]=1.03) was identified as a predictor of advanced tumor stage (≥pT3) in the overall population. However, only leptin remained an independent predictive factor for advanced tumor stage (≥pT3) (OR=1.15) in patients with obesity. CONCLUSIONS: In conclusion, our results indicate that a higher leptin level in obese men can be considered a risk factor for aggressive PCa. This prospective study provides greater insight into the role of circulating adipokines in Korean patients with PCa undergoing RP, particularly in patients with obesity.
Adipokines ; Adiponectin ; Body Mass Index ; Humans ; Incidence ; Insulin-Like Growth Factor I ; Interleukin-2 ; Leptin ; Logistic Models ; Male ; Multivariate Analysis ; Neoplasm Grading ; Obesity ; Passive Cutaneous Anaphylaxis ; Prospective Studies ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Resistin ; Risk Factors

OBJECTIVE: The present study aims to analyze the levels of resistin, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-18, and C-reactive protein (CRP) in patients with Alzheimer's disease (AD) and also investigate a potential relationship between resistin levels and TNF-α, IL-1β, IL-6, IL-18, and CRP levels in patients with AD. METHODS: The study included fifty patients with AD and 30 healthy controls with normal cognitive functions. The serum resistin, TNF-α, IL-1β, IL-6, IL-18, and CRP levels were assessed. We performed a Mini-Mental State Examination (MMSE) to evaluate the general cognitive performance. RESULTS: The mean serum resistin, IL-1β, IL-18, and TNF-α levels were significantly higher in patients with AD compared with the controls (p=0.026, p=0.002, p=0.003, and p=0.038, respectively). The IL-6 and CRP levels did not differ between the groups (p=0.874 and p=0.941). The resistin levels were positively correlated with the levels of CRP and IL-18 (r=0.526, p<0.001; r=0.402, p=0.004, respectively). MMSE scores and inflammatory markers were not correlated (p>0.05 for all). CONCLUSION: Serum resistin levels were significantly increased and correlated with some inflammatory markers in AD patients, suggesting that resistin might play a role in the inflammatory process of AD.
Alzheimer Disease* ; C-Reactive Protein ; Cognition ; Cytokines* ; Humans ; Inflammation ; Interleukin-18 ; Interleukin-6 ; Interleukins ; Resistin* ; Tumor Necrosis Factor-alpha

Adipose tissue secretes a variety of bioactive substances that are associated with chronic inflammation, insulin resistance, and an increased risk of type 2 diabetes mellitus. While resistin was first known as an adipocyte-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents, it is predominantly expressed and secreted by macrophages in humans. Epidemiological and genetic studies indicate that increased resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. Resistin also appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and the formation of foam cells. Thus, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with cardiovascular disease and heart failure. Furthermore, recent evidence suggests that resistin is associated with atherogenic dyslipidemia and hypertension. The present review will focus on the role of human resistin in the pathogeneses of inflammation and obesity-related diseases.
Adipose Tissue ; Arteritis ; Atherosclerosis ; Cardiovascular Diseases ; Cell Proliferation ; Diabetes Mellitus, Type 2 ; Dyslipidemias ; Foam Cells ; Heart Failure ; Humans ; Hypertension ; Inflammation* ; Insulin Resistance ; Macrophages ; Muscle, Smooth, Vascular ; Obesity ; Resistin* ; Rodentia

β-cell failure coupled with insulin resistance plays a key role in the development of type 2 diabetes mellitus (T2DM). Changed adipokines in circulating level form a remarkable link between obesity and both β-cell failure and insulin resistance. Some adipokines have beneficial effects,whereas others have detrimental properties. The overall contribution of adipokines to β-cell failure mainly depends on the interactions among adipokines. This article reviews the role of individual adipokines such as leptin,adiponectin,and resistin in the function,proliferation,death,and failure of β-cells. Future studies focusing on the combined effects of adipokines on β-cells failure may provide new insights in the treatment of T2DM.
Adipokines ; metabolism ; Adiponectin ; metabolism ; Diabetes Mellitus, Type 2 ; physiopathology ; Humans ; Insulin Resistance ; Insulin-Secreting Cells ; pathology ; Leptin ; metabolism ; Obesity ; Resistin ; metabolism

Resistin is a new adipokine found in vivo in recent years. Recent studies have indicated that resistin contributes to the development of insulin resistance and type 2 diabetes mellitus (T2DM) and mediates inflammatory reaction via different signal pathways. As a signal factor between inflammation and metabolism, resistin is expected to provide new insights for the treatment of insulin resistance and T2DM. However, because specific receptor of resistin has not been identified in the body so far, the molecular mechanism of resistin actions is still unclear. In this article, we review the latest progresses of resistin study, especially the role of resistin in insulin resistance and its signaling mechanism.
Diabetes Mellitus, Type 2 ; Humans ; Inflammation ; Insulin Resistance ; Resistin ; Signal Transduction

OBJECTIVE: We aimed to investigate the relationship between adipokines and antioxidation enzyme and the risk of progression of symptomatic intracranial atherosclerotic stenosis (ICAS). METHODS: Of 409 patients who participated in the TOSS-2 (trial of cilostazol in symptomatic intracranial stenosis-2) study, 52 patients showed progression of symptomatic ICAS on magnetic resonance angiography at seven months after an index stroke. We randomly selected 20 patients with progression and 20 age- and sex-matched control patients. We serially collected blood sample initially, one month, and seven months after an index stroke. Then, multiplex analysis of biomarkers was performed for adiponectin, resistin, leptin, and superoxide dismutase-1, 2, 3. RESULTS: Demographic features and risk factors such as hypertension, diabetes, and smoking history were comparable between the two groups. Control group showed higher adiponectin levels at 7 months than progression group (P=0.05) and a significant in-creasing trend (P for trend=0.01). Resistin, leptin, and superoxide dismutase-1, 2, 3 levels were not different between the progression and control group initially, one month, and seven months after an index stroke. CONCLUSION: Increase of adiponectin level showed protective effect in the progression of ICAS. Resistin, leptin, and superoxide dismutase-1, 2, 3 levels are not different between the groups. Further large numbers of patients with longer follow-up studies are needed.
Adipokines* ; Adiponectin ; Biomarkers ; Constriction, Pathologic* ; Follow-Up Studies ; Humans ; Hypertension ; Leptin ; Magnetic Resonance Angiography ; Resistin ; Risk Factors ; Smoke ; Smoking ; Stroke ; Superoxide Dismutase ; Superoxides*

BACKGROUND: Systemic inflammation in psoriasis causes insulin resistance and cardiovascular diseases. Adipokines are adipose-tissue-derived factors that are involved in metabolic processes. It is thought that these adipokines are associated with the development of psoriasis. OBJECTIVE: The purpose of this study was to determine the changes in adipokine levels, insulin resistance, hypertension, and dyslipidemia over a 12-week period. METHODS: The study comprised 35 psoriasis patients and 50 controls. Blood samples were obtained twice from the patients, one sample at the start and one at the end of a 12-week follow-up period. The following parameters were assessed in both groups: serum fasting glucose, fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, serum lipids, adiponectin, leptin, resistin, chemerin, omentin, vaspin, visfatin, retinol-binding protein 4, and high-sensitivity C-reactive protein (hs-CRP) levels; blood pressure; body mass index; and the psoriasis area severity index (PASI) scores. RESULTS: The patients showed an improvement in the PASI score and a significant decrease in serum hs-CRP, omentin, and chemerin values. Moreover, at the start of the follow-up, the psoriasis patients had significantly lower levels of adiponectin and visfatin and significantly higher levels of vaspin and resistin than those of the control group. Visfatin levels correlated negatively with low-density lipoprotein (LDL) and cholesterol, while vaspin and omentin levels correlated positively with diastolic blood pressure. Decreased adiponectin levels correlated negatively with diastolic blood pressure and LDL. CONCLUSION: Plasma levels of adipokines might be useful for evaluating the disease activity of psoriasis and its comorbidities.
Adipokines* ; Adiponectin ; Blood Pressure ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Cholesterol ; Comorbidity ; Dyslipidemias* ; Fasting ; Follow-Up Studies ; Glucose ; Homeostasis ; Humans ; Hypertension* ; Inflammation ; Insulin Resistance* ; Insulin* ; Leptin ; Lipoproteins ; Metabolism ; Nicotinamide Phosphoribosyltransferase ; Plasma ; Psoriasis* ; Resistin

OBJECTIVETo investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system.

METHODSForty-five male Sprague-Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses.

RESULTSCompared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (P<0.01). The levels of serum resistin, and of resistin protein and mRNA in liver, were significantly higher in the MC group than in the NC group of rats (all P less than 0.01). The body weight of rats in the TP group was significantly lower than those in the MC group (P<0.05). The levels of serrn resistin, resistin protein and mRNA in the liver, and insulin resistance were significantly lower in the TP group than in the MC group of rats (all P<0.01). The PP group did not show significant differences in any of these measures, except for loss of body weight (P<0.05).

CONCLUSIONTelmisartan elicits preventive and protective effects in a NASH rat model.Telmisartan may improve insulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA.

Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Benzimidazoles ; Benzoates ; Cholesterol ; Diet, High-Fat ; Disease Models, Animal ; Insulin ; Insulin Resistance ; Male ; Non-alcoholic Fatty Liver Disease ; Rats ; Rats, Sprague-Dawley ; Resistin ; Triglycerides