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Background: Excessive subcutaneous adiposity in obesity is associated to positive white adipocyte tissue (WAT) differentiation (adipogenesis) and WAT expandability. Here, we hypothesized that supplementation with the insulin inhibitor and mitochondrial uncoupler, Tyrphostin (T-AG17), in vitro and in vivo inhibits adipogenesis and adipocyte hypertrophy. Methods: We used a 3T3-L1 proadipocyte cell line to identify the potential effect of T-AG17 on adipocyte differentiation and fat accumulation in vitro. We evaluated the safety of T-AG17 and its effects on physiological and molecular metabolic parameters including hormonal profile, glucose levels, adipogenesis and adipocyte hypertrophy in a diet-induced obesity model using C57BL/6 mice. Results: We found that T-AG17 is effective in preventing adipogenesis and lipid synthesis in the 3T3-L1 cell line, as evidenced by a significant decrease in oil red staining (p < 0.05). In obese C57BL/6 mice, oral administration of T-AG17 (0.175 mg/kg for 2 weeks) lead to decreased fat accumulation and WAT hypertrophy. Further, T-AG17 induced adipocyte apoptosis by activating caspase-3. In the hepatocytes of obese mice, T-AG17 promoted an increase in the size of lipid inclusions, which was accompanied by glycogen accumulation. T-AG17 did not alter serum biochemistry, including glucose, insulin, leptin, free fatty acids, creatinine, and aspartate aminotransferase. Conclusion: T-AG17 promotes adipocyte apoptosis in vivo and is an effective modulator of adipocyte differentiation and WAT hypertrophy in vitro and in vivo. Therefore, T-AG17 may be useful as a pharmacological obesity treatment. [ABSTRACT FROM AUTHOR]

An in silico study was carried out to identify antigens for their possible collective use as vaccine candidates against diseases caused by different classes of pathogenic mycobacteria with significant clinical relevance. The genome sequences of the relevant causative agents were used in order to search for orthologous genes among them. Bioinformatics tools permitted us to identify several conserved sequences with 100% identity with no possibility of cross-reactivity to the normal flora and human proteins. Nine different proteins were characterized using the strain H37Rv as reference and taking into account their functional category, their in vivo expression and subcellular location. T and B cell epitopes were identified in the selected sequences. Theoretical prediction of population coverage was calculated for individual epitopes as well as their combinations. Several identical sequences, belonging to six proteins containing T and B cell epitopes which are not present in selected microorganisms of the normal microbial flora or in human proteins were obtained. [ABSTRACT FROM AUTHOR]