Does reversible cysteine oxidation link the Western diet to cardiac dysfunction?

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, ß-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.

Prevalence of metabolic syndrome in Gwalior region of Central India: A comparative study using NCEP ATP III, IDF and Harmonized criteria.

BACKGROUND: The aim of this study is to determine the prevalence of Metabolic syndrome (MetS) in the people of Gwalior. Three criteria viz., National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, International Diabetes Federation (IDF) criteria and Harmonized criteria for MetS were employed to assess the prevalence of metabolic syndrome in this region, their concordance with respect to this population was recorded. METHODS: The cross-sectional study involved the people, who had attended the Diabetes clinic at the Centre for Translational Research, Jiwaji University during 2015-2017. A total of 1190 participants within the age group of 20-79 years of either gender were included in the study. Anthropometric parameters, blood pressure, blood glucose and lipid profile of all subjects were assessed. Student's 't' test, Kappa statistics and Binary logistic regression model were used to analyze the data. RESULTS: The percentage of prevalent MetS was found to be 72.7, 50.2 and 53.9 following Harmonized criteria, NCEP ATPIII and IDF criteria respectively. The prevalence was found to be maximum in centrally obese female population, aged between 51 and 60 years with the presence of hyperglycemia and reduced HDL- C. Harmonized and IDF criteria showed good agreement (κ 0.85). Regression analysis showed that, high body mass index, hypertension and dyslipedimia were the most critical predictive risk factors of MetS. CONCLUSIONS: Maximum prevalence of MetS was recorded when the Harmonized criteria was followed. A good agreement was observed between Harmonized vs. IDF criteria. MetS if detected early especially in apparently healthy subjects; paves way for preventive measures to be designed in order to avert the incidence of diabetes and other risks related to cardio vascular disease.

Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes.

UNLABELLED: 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 downregulated expression of aP2, PPARgamma, leptin, and C/EBPalpha. 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/EBPalpha 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.

Chitosan encapsulated nanocurcumin induces GLUT-4 translocation and exhibits enhanced anti-hyperglycemic function.

AIM: The present study was undertaken to develop a Curcumin nanoparticle system with chitosan as a hydrophilic carrier. In addition, the anti-diabetic potential of curcumin loaded chitosan nanoparticles were assessed in comparison to those of free curcumin by examining the anti-hyperglycemic efficacy using in vitro assays. METHODS: Curcumin loaded chitosan nanoparticles were prepared and characterized for particle size by transmission electron microscopy, FT-IR, differential scanning calorimetry and therapeutic effects of curcumin loaded chitosan nanoparticles were evaluated by measuring the level of GLUT-4 present at the plasma membrane in L6myc myotubes followed by western blotting. Additionally, anti-inflammatory potential of curcumin loaded chitosan nanoparticles were assessed by enzyme immunoassay using appropriate ELISA kits. KEY FINDINGS: Transmission electron microscopy revealed an average nanocurcumin particle size of 74 nm. Under in vitro conditions, treatment with chitosan-nanocurcumin (CS-NC) caused a substantial increase in the GLUT-4 translocation to the cell surface in L6 skeletal muscle cells and the effect was associated with increased phosphorylation of AKT (Ser-473) and its downstream target GSK-3ß (Ser-9). SIGNIFICANCE: The therapeutic potential of nanocurcumin is prominent than that of curcumin alone. Nanocurcumin could improve the solubility of curcumin and may prolong its retention in the systemic circulation.

Bougainvillea spectabilis Exhibits Antihyperglycemic and Antioxidant Activities in Experimental Diabetes.

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.

Combined administration of testosterone plus an ornithine decarboxylase inhibitor as a selective prostate-sparing anabolic therapy.

Because of its anabolic effects on muscle, testosterone is being explored as a function-promoting anabolic therapy for functional limitations associated with aging; however, concerns about testosterone's adverse effects on prostate have inspired efforts to develop strategies that selectively increase muscle mass while sparing the prostate. Testosterone's promyogenic effects are mediated through upregulation of follistatin. We show here that the administration of recombinant follistatin (rFst) increased muscle mass in mice, but had no effect on prostate mass. Consistent with the results of rFst administration, follistatin transgenic mice with constitutively elevated follistatin levels displayed greater muscle mass than controls, but had similar prostate weights. To elucidate signaling pathways regulated differentially by testosterone and rFst in prostate and muscle, we performed microarray analysis of mRNAs from prostate and levator ani of castrated male mice treated with vehicle, testosterone, or rFst. Testosterone and rFst shared the regulation of many transcripts in levator ani; however, in prostate, 593 transcripts in several growth-promoting pathways were differentially expressed after testosterone treatment, while rFst showed a negligible effect with only 9 transcripts differentially expressed. Among pathways that were differentially responsive to testosterone in prostate, we identified ornithine decarboxylase (Odc1), an enzyme in polyamine biosynthesis, as a testosterone-responsive gene that is unresponsive to rFst. Accordingly, we administered testosterone with and without α-difluoromethylornithine (DFMO), an Odc1 inhibitor, to castrated mice. DFMO selectively blocked testosterone's effects on prostate, but did not affect testosterone's anabolic effects on muscle. Co-administration of testosterone and Odc1 inhibitor presents a novel therapeutic strategy for prostate-sparing anabolic therapy.