遗传资源与进化国家重点实验室知识库

Background/Aims: Abnormal fatty acid β oxidation has been associated with obesity andtype 2 diabetes. Resistin is an adipokine that has been considered as a potential factor inobesity-mediated insulin resistance and type 2 diabetes. However, the effect of resistin onfatty acid β oxidation needs to be elucidated. Methods: We detected the effects of resistinon the expression of fatty acid oxidation (FAO) transcriptional regulatory genes, the fatty acidtransport gene, and mitochondrial β-oxidation genes using real-time PCR. The rate of FAOwas measured using  14 C-palmitate. Immunofluorescence assay and western blot analysis wereused to explore the underlying molecular mechanisms. Results: Resistin leads to a reductionin expression of the FAO transcriptional regulatory genes ERRα and NOR1, the fatty acidtransport gene CD36, and the mitochondrial β-oxidation genes CPT1, MCAD, and ACO.Importantly, treatment with resistin led to a reduction in the rate of cellular fatty acid oxidation.In addition, treatment with resistin reduced phosphorylation of acetyl CoA carboxylase (ACC)(inhibitory). Mechanistically, resistin inhibited the activation of CREB, resulting in suppressionof PGC-1α. Importantly, overexpressing PGC-1α can rescue the inhibitory effects of resistin onfatty acid β oxidation. Conclusions: Activating the transcriptional activity of CREB using smallmolecular chemicals is a potential pharmacological strategy for preventing the inhibitoryeffects of resistin on fatty acid β oxidation.