Abstract
Uncoupling protein 3 (UCP3) is a mitochondrial membrane transporter that is expressed mainly in skeletal muscle where it plays an important role in energy expenditure and fat oxidation. In this study, we investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on UCP3 gene expression in C2C12 muscle cells. EPA and DHA up-regulated UCP3 mRNA level in a dose-dependent manner and similarly increased UCP3 promoter activity in C2C12 muscle cells. To determine whether AMP-activated protein kinase (AMPK) signaling may also directly regulate UCP3 expression, 5′-amino-4-imidazolecarboxamide-ribonucleoside (AICAR), an AMP analog that activates AMPK, was treated in C2C12 muscle cells. AICAR showed additive effects with EPA or DHA on the UCP3 promoter activation. These results indicate that EPA and DHA directly regulate the gene expression of UCP3, potentially through AMPK-mediated pathway in C2C12 muscle cells.
Highlights
Uncoupling protein (UCP) 1, 2, and 3 are mitochondrial inner membrane proteins that allow dissipation of part of the proton electrochemical gradient generated by the electron transfer chain across the mitochondrial inner membrane, increasing heat production by uncoupling respiration from adenosine triphosphate (ATP) synthesis [1]
UCP2 is widely expressed in several tissues of the body, whereas Uncoupling protein 3 (UCP3) is expressed at high levels in skeletal muscle as well as in brown adipose tissue (BAT) [4]
The present study investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on UCP3 gene expression in C2C12 muscle cells
Summary
Uncoupling protein (UCP) 1, 2, and 3 are mitochondrial inner membrane proteins that allow dissipation of part of the proton electrochemical gradient generated by the electron transfer chain across the mitochondrial inner membrane, increasing heat production by uncoupling respiration from adenosine triphosphate (ATP) synthesis [1]. The amino acid sequence of UCP1 is 59% and 57%. Identical to the sequence of UCP2 and UCP3, respectively [2]. UCP1 is expressed mainly in brown adipose tissue, which plays an important role in the maintenance of energy balance and thermogenesis induced by cold [3]. UCP2 is widely expressed in several tissues of the body, whereas UCP3 is expressed at high levels in skeletal muscle as well as in brown adipose tissue (BAT) [4]. UCP2 and UCP3 are not generally responsible for thermogenesis, but they might be significantly thermogenic when activated fully by endogenous or exogenous environmental effectors [5]. Skeletal muscle plays important role in the energy expenditure by activation of uncoupling proteins
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