title: UCP4 overexpression improves fatty acid oxidation and insulin sensitivity in L6 myocytes.
abstract: Obesity, which is caused by energy uptake being greater than energy expenditure, is widely prevalent today. Currently, only a limited number of efficient interventional strategies are available for the prevention of obesity. Previous studies have shown that UCP4 transcription occurs at a considerable level in mouse skeletal muscle; however, the exact functions of UCP4 remain unclear. In this study, we investigated the effect of UCP4 on mitochondrial function and insulin sensitivity in mature L6 myocytes. UCP4 overexpression in L6 myocytes induced increased mitochondrial carnitine palmitoyltransferase 1A (CPT1A) and decreased citrate synthase (CS) mRNA in the basal condition (i.e., in the absence of insulin). UCP4 overexpression significantly improved insulin sensitivity, increased tyrosine phosphorylation of IRS-1 in the presence of insulin, and significantly reduced intracellular triglyceride (TG). Additionally, intracellular ATP content and mitochondrial membrane potential were downregulated. We also observed that intracellular ROS, mitochondrial morphology, and mitochondrial mtDNA copy number were maintained upon UCP4 expression, with no change in mitochondrial fusion and fission. In summary, our findings provide evidence to show that UCP4 overexpression reduced the insulin sensitivity and mitochondrial fatty acid oxidation of L6 myocytes. These findings support the notion that UCPs are ideal targets for treatment of insulin resistance.
authors: Department of Pediatrics, Jinling Hospital, Nanjing, China.
authors: Chun-Lin
authors: CL
authors: Gao
authors: Yu-Hui
authors: YH
authors: Ni
authors: Guanglin
authors: G
authors: Liu
authors: Xiao-Hui
authors: XH
authors: Chen
authors: Chen-Bo
authors: CB
authors: Ji
authors: Da-Ni
authors: DN
authors: Qin
authors: Chun-Zhao
authors: CZ
authors: Kou
authors: Chun
authors: C
authors: Zhu
authors: Chun-Mei
authors: CM
authors: Zhang
authors: Zheng-Kun
authors: ZK
authors: Xia
authors: Xi-Rong
authors: XR
authors: Guo
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