The mechanisms by which androgens regulate fat mass are poorly understood. Although testosterone has been reported to increase lipolysis and inhibit lipid uptake, androgen effects on proliferation and differentiation of human mesenchymal stem cells (hMSCs) and preadipocytes have not been studied. Here, we investigated whether dihydrotestosterone (DHT) regulates proliferation, differentiation, or functional maturation of hMSCs and human preadipocytes from different fat depots. DHT (0-30 nM) dose-dependently inhibited lipid accumulation in adipocytes differentiated from hMSCs and downregu-lated expression of aP2, PPARγ, leptin, and C/EBPα. Bicalutamide attenuated DHT's inhibitory effects on adipogenic differentiation of hMSCs. Adipocytes differentiated in presence of DHT accumulated smaller oil droplets suggesting reduced extent of maturation. DHT decreased the incorporation of labeled fatty acid into triglyceride, and downregulated acetyl CoA carboxylase and DGAT2 expression in adipocytes derived from hMSCs. DHT also inhibited lipid accumulation and downregulated aP2 and C/EBPα in human subcutaneous, mesenteric and omental preadipocytes. DHT stimulated forskolin-stimulated lipolysis in subcutaneous and mesenteric preadipocytes and inhibited incorporation of fatty acid into triglyceride in adipocytes differentiated from preadipocytes from all fat depots.Conclusions-DHT inhibits adipogenic differentiation of hMSCs and human preadipocytes through an AR-mediated pathway, but it does not affect the proliferation of either hMSCs or preadipocytes. Androgen effects on fat mass represent the combined effect of decreased differentiation of fat cell precursors, increased lipolysis, and reduced lipid accumulation.
Using a novel cysteine thiol labeling strategy coupled with mass spectrometric analysis, we identified and quantified the changes in global reversible cysteine oxidation of proteins in the left ventricle of hearts from mice with metabolic syndrome-associated diastolic dysfunction. This phenotype was induced by feeding a high-fat, high-sucrose, type-2 diabetogenic diet to C57BL/6J mice for 8 mo. The extent of reversible thiol oxidation in relationship to the total available (free and reducible) level of each cysteine could be confidently determined for 173 proteins, of which 98 contained cysteines differentially modified ≥1.5-fold by the diet. Our findings suggest that the metabolic syndrome leads to potentially deleterious changes in the oxidative modification of metabolically active proteins. These alterations may adversely regulate energy substrate flux through glycolysis, β-oxidation, citric acid (TCA) cycle, and oxidative phosphorylation (oxphos), thereby contributing to maladaptive tissue remodeling that is associated with, and possibly contributing to, diastolic left ventricular dysfunction.
The study investigates the effects of aqueous extract of Bougainvillea spectabilis leaves on blood glucose, glycosylated hemoglobin, lipid profile, oxidative stress, and on DNA damage, if any, as well as on liver and kidney functions in streptozotocin-induced diabetes in Wistar rats. Daily administration of the aqueous extract of B spectabilis leaves for 28 days resulted in significant reduction in hyperglycemia and hyperlipidemia as evident from restoration of relevant biochemical markers following extract administration. The extract also exhibited significant antioxidant activity as evidenced from the enzymatic and nonenzymatic responses and DNA damage markers. The extract restored kidney and liver functions to normal and proved to be nontoxic. A marked improvement in the histological changes of tissues was also observed. The present study documented antihyperglycemic, antihyperlipidemic, and antioxidative potentials of the aqueous extract of B spectabilis leaves without any toxicity in streptozotocin-treated Wistar rats.
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