Regulation of adiponectin secretion in human subcutaneous and omental adipose tissue: effects of pioglitazone and endothelin-1: a pilot study.

OBJECTIVE: The study was designed to test the effect of anti-diabetic agent pioglitazone and Endothelin-1 (ET-1) on adiponectin secretion from human adipose tissue in depot dependent manner. METHODS: Subcutaneous adipose tissue (SAT) and omental adipose tissues (OAT) were obtained from 19 subjects, including 6 non-obese controls, 7 obese and 6 obese T2DM patients. Adipose tissue was treated with pioglitazone and ET1. Adiponectin secreted into the culture medium after treatment at different time interval (0, 24, 48, 96 hours) was determined by ELISA and normalized for cellular DNA content. RESULTS: Basal adiponectin secretion from both the depots significantly associated with serum adiponectin, BMI, waist and HOMA-IR. Though no depot-specific difference was found in adiponectin secretion from SAT and OAT in our population, significant reduction in adiponectin secretion was observed in SAT of obese and T2DM patients compared to controls. Responsiveness to pioglitazone treatment was more in SAT, while ET1 inhibits adiponectin secretion in OAT. CONCLUSION: These data suggest that, SAT, appears to be major contributor to regulation of adiponectin in circulation. Pioglitazone stimulate adiponectin secretion in SAT compared to OAT in diabetic patients while ET-1 inhibiting adiponectin secretion in OAT of diabetic patients. We need to focus on mechanism underlying these regulatory agents mediated stimulation or inhibition of adiponectin secretion in human adipose tissue.

Association between adipocytokines and insulin resistance in Indian hypertensive patients.

OBJECTIVE: Although the relationship between obesity, hypertension (HT), and insulin resistance is well-recognised, the pathophysiological mechanism involved is relatively poorly understood. The present study aims in examining the relationship between adipocytokines and insulin resistance in Indian hypertensive patients to better understand the pathogenesis of HT. METHODS: A total of 124 subjects including 41 controls, 41 obese, and 42 hypertensive patients were recruited in this cross-sectional study. Fasting adipocytokines (leptin, adiponectin, resistin) and highly sensitive C-reactive protein (hsCRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Insulin resistance (IR) index was calculated by the homeostasis model assessment (HOMA). The relation between these variables was studied by univariate and multiple logistic regression analysis. RESULTS: Among the hypertensive patients, obese hypertensive patients exhibited significantly increased HOMA-IR and altered adipocytokine profile compared to the non-obese control subjects. In a stepwise multiple linear regression analysis with IR as a dependant variable, the study shows leptin as a significant predictor in hypertensive patients. Multiple logistic regression analysis revealed that among the adipocytokines, leptin had a strong association with HT in our population. CONCLUSION: Among the adipocytokine, serum leptin levels were significantly increased in hypertensive patients and were also associated with IR and HT. Thus, our findings suggest that leptin may be playing an important role in the development of HT in our population.

Uncoupling protein-2 (UCP2) gene expression in subcutaneous and omental adipose tissue of Asian Indians: Relationship to adiponectin and parameters of metabolic syndrome.

OBJECTIVE: UCP2 is a mitochondrial membrane transporter expressed in white adipose tissue and involved in regulation of energy balance. In this present study, we examined the depot specific comparison of UCP2 gene expression in different metabolic states, in order to explore the potential role of UCP2 in human obesity and diabetes. We also determined UCP2's association with adiponectin and insulin resistance with different parameters of the metabolic syndrome. METHODS: Subcutaneous adipose tissue (SAT) and omental adipose tissues (OAT) were obtained from 69 subjects, including 23 non-obese controls, 26 obese and 20 obese T2DM patients. Metabolic syndrome and other clinical features were studied. Adiponectin and UCP2 gene expression was quantitated by Real Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). RESULTS: UCP2 gene expression was significantly reduced in obese and diabetic patients compared with controls. Interestingly, we found that UCP2 gene expression was reduced more in omental fat compared with subcutaneous fat and this effect was observed only in males but not in females. Partial correlation analysis showed significant association with the obesity parameters waist circumference, insulin and HOMA-IR, the lipid parameter triglyceride and the adipokine adiponectin. CONCLUSION: Reduced UCP2 gene expression in obese and diabetic patients and its association with obesity parameters and HOMA-IR confirms its role as a candidate gene in the study of obesity and diabetes in our population. Also, its association with triglycerides implicates its role in lipid metabolism. An association between adiponectin and UCP2 gene expression may provide us with an innovative therapeutic strategy to prevent obesity related diseases, like diabetes and CVD.

Association of adiposity, inflammation and atherosclerosis: the role of adipocytokines and CRP in Asian Indian subjects.

BACKGROUND: To reveal the exact link between adipose tissue, inflammation, and cardiovascular disease (CVD), we studied the association of C-reactive protein (CRP) with insulin resistance and adipocytokines in Asian Indian subjects. METHODS: Forty-one controls, 40 obese, and 53 type 2 diabetes (T2DM) patients (total 134) were recruited. Enzyme-linked immunoassay (ELISA) technique was used to determine serum CRP and adipocytokine concentrations. Serum insulin was measured by radioimmune assay, and insulin resistance index was calculated by the homeostasis model assessment (HOMA). Association of CRP with different adipocytokines and insulin resistance was assessed with univariate regression analysis. RESULTS: Serum leptin, resistin, and CRP levels were significantly increased and adiponectin levels were significantly reduced in obese subjects. In T2DM patients, CRP levels were increased and adiponectin levels were significantly decreased but no difference in leptin and resistin levels were found compared to controls. An important finding of this study was the significantly reduced levels of leptin, adiponectin, and resistin in nonobese T2DM patients compared to their BMI-matched controls. CRP in all subjects showed a significant correlation with obesity parameters like BMI (P < 0.001), waist circumference (P < 0.01), body fat percentage (P < 0.01), HOMA-IR (P < 0.001), leptin (P < 0.05), and resistin (P < 0.01). CONCLUSIONS: The association of CRP with insulin resistance, adipocytokines, and resistin reveals close links between inflammation, CVD, and adipose tissue. These findings provide an exciting therapeutic opportunity in cardiovascular disease by targeting various proinflammatory cascades in adipocytes.