RESUMO
Rosmarinic acid (RA), a polyphenol, is known to improve hepatic insulin sensitivity in experimental type 2 diabetes. However, its effect on skeletal muscle insulin resistance is meagerly understood. The present study was aimed to investigate the up- and downstream mediators of the molecular targets of RA in attenuating insulin resistance in the skeletal muscle both in vivo and in vitro. We found that supplementation of RA increased the expression of key genes involved in the mitochondrial biogenesis like PGC-1α, SIRT-1, and TFAM via activation of AMPK in the skeletal muscle of insulin resistant rats as well as in L6 myotubes. Further, RA treatment increased the glucose uptake and decreased the phosphorylation of serine IRS-1 while increasing the translocation of GLUT 4. Together, our findings evidenced that RA treatment significantly inhibit insulin resistance in skeletal muscle cells by enhancing mitochondrial biogenesis. J. Cell. Biochem. 118: 1839-1848, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cinamatos/farmacologia , Depsídeos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Ratos , Ratos Wistar , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ácido RosmarínicoRESUMO
Acrylamide (ACR) is a known industrial toxic chemical that produce neurotoxicity characterized by progressive neuronal degeneration. This study was designed to investigate the protective effect of fish oil on ACR-induced neuronal damage in Wistar rats. ACR enhances the production of reactive oxygen species and potentially affects brain. ACR administered rats showed increased levels of lipid peroxidative product, protein carbonyl content, hydroxyl radical and hydroperoxide which were significantly modulated by the supplementation of fish oil. The activities of enzymic antioxidants and levels of reduced glutathione were markedly lowered in ACR-induced rats; fish oil treatment augmented these antioxidant levels in cortex. Free radicals generated during ACR administration reduced the activities of membrane adenosine triphosphatases and acetylcholine esterase. Fish oil enhanced the activities of these enzymes near normal level. Histological observation represented the protective role of fish oil in ACR-induced neuronal damage. Fish oil reduced the ACR-induced apoptosis through the modulation in expressions of B-cell lymphoma 2 (Bcl2)-associated X protein and Bcl2-associated death promoter. Further, fish oil increases the expression of heat shock protein 27 (Hsp27) in ACR-induced rats. This study provides evidence for the neuroprotective effect of fish oil on ACR-induced neurotoxicity by reducing oxidative stress and apoptosis with modulation in the expression of Hsp27.
