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Effects of eicosapentaenoic acid and docosahexaenoic acid on uncoupling protein 3 gene expression in C(2)C(12) muscle cells.

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 C(2)C(12) muscle cells. EPA and DHA up-regulated UCP3 mRNA level in a dose-dependent manner and similarly increased UCP3 promoter activity in C(2)C(12) 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 C(2)C(12) 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 C(2)C(12) muscle cells.

SUBMITTER: Lee MS

PROVIDER: S-EPMC3708343 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Effects of eicosapentaenoic acid and docosahexaenoic acid on uncoupling protein 3 gene expression in C(2)C(12) muscle cells.

Lee Mak-Soon MS Kim In-Hwan IH Kim Yangha Y

Nutrients 20130521 5

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 C(2)C(12) muscle cells. EPA and DHA up-regulated UCP3 mRNA level in a dose-dependent manner and similarly increased UCP3 promoter activity in C(2)C(12) muscle cells. To determine whe ...[more]

PMID: 23698161

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Project description:The objectives of this study were to evaluate the effect of feeding an enriched diet with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to finishing lambs born from ewes supplemented either with or without EPA and DHA during late gestation on productive performance, muscle fatty acid (FA), and hypothalamus mRNA concentration of metabolic genes and hormone receptors. Lambs born from dams fed during the last 50 d of gestation either with a control diet containing 0.39% Ca salts of palmitic fatty acid distillate (C) or Ca salts enriched with EPA and DHA (PFA) were used. After weaning lambs (n = 70) were blocked by weight (BW) and used in a 2 × 2 factorial into 2 finishing diets containing 1.5% of C or PFA. The 2 factors were the ewe diet and the finishing diet. Lambs (37.9 ± 0.4 kg) were weighed and blood sampled for glucose and NEFA measurements at days 1, 14, 28, and 42. Dry matter intake (DMI) was measured daily. At day 43, 14 females and 14 males were slaughtered, and hot carcass weight, body wall thickness, rib eye area, and FA composition of Longissumus thoracis muscle were evaluated. Female hypothalamuses were obtained and mRNA concentration of hormone receptors, neuropeptides, and their receptors was measured. Lambs born from PFA dams were heavier (P < 0.01). There was a time × finishing diet interaction for BW (P = 0.03), and lambs fed C had a greater BW. Lambs fed C had an increase in DMI (P < 0.01). There were no significant differences in plasma glucose and NEFA concentration (P > 0.1). Lambs born from PFA dams had a greater concentration of C22:0 (P < 0.03). Lambs fed C had higher concentrations of C18:1c15 (P < 0.01), C17:0 (P < 0.09), C18:0 (P < 0.09), and n6/n3 (P < 0.01). Lambs fed PFA had greater concentration (P < 0.05) of C16:1, C22:1, C20:5, C22:5, C22:6, total n3 FA, and total EPA and DHA. There was a significant dam × finishing diet interaction (P ≤ 0.08) on mRNA concentration for MCR3, CCK-R, Cort-R, and CART. Lambs, which had the same treatment as their dams, showed lower overall mRNA concentration than those with different treatments between them and their dams. Lambs born from PFA ewes had lower concentration of MCR4 mRNA (P = 0.09) than C. Agouti-related peptides mRNA concentration was lower in lambs fed PFA (P = 0.06) than C. In conclusion, changes on lamb performance, muscle fatty acid composition, and metabolic neuropeptides depend not only on the lamb diet, but also on the dam diet during late gestation.

Project description:Polyunsaturated fatty acids are important nutrients for human health, especially omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have been found to play positive roles in the prevention of various diseases. However, previous studies have reported that excessive omega-3 fatty acids supplement during pregnancy caused side effects such as slower neural transmission times and postnatal growth restriction. In this study, we investigated the effect of EPA and DHA on mitochondrial function and gene expression in C2C12 myoblasts during skeletal muscle differentiation. C2C12 myoblasts were cultured to confluency and then treated with differentiation medium that contained fatty acids (50-µM EPA and DHA). After 72?h of myogenic differentiation, mRNA was collected, and gene expression was analyzed by real-time PCR. Microscopy was used to examine cell morphology following treatment with fatty acids. The effect of EPA and DHA on cellular oxygen consumption was measured using a Seahorse XF24 Analyzer. Cells treated with fatty acids had fewer myotubes formed (P ? 0.05) compared with control cells. The expression of the genes related to myogenesis was significantly lower (P ? 0.05) in cells treated with fatty acids, compared with control cells. Genes associated with adipogenesis had higher (P ? 0.05) expression after treatment with fatty acids. Also, the mitochondrial biogenesis decreased with lower (P ? 0.05) gene expression and lower (P ? 0.05) mtDNA/nDNA ratio in cells treated with fatty acids compared with control cells. However, the expression of genes related to peroxisome biosynthesis was higher (P ? 0.05) in cells treated with fatty acids. Moreover, fatty-acid treatment reduced (P ? 0.05) oxygen consumption rate under oligomycin-inhibited (reflecting proton leak) and uncoupled conditions. Our data imply that fatty acids might reduce myogenesis and increase adipogenesis in myotube formation. Fatty acids may also decrease cell metabolism by reducing mitochondrial biogenesis as well as respiration rate. This study suggests that the maternal overdosage of EPA and DHA may influence fetal muscle development, increase intramuscular adipose tissue deposition in offspring, and have a long-term effect on the development of metabolic diseases such as obesity and diabetes in adult offspring.

Dataset Information

Effects of eicosapentaenoic acid and docosahexaenoic acid on uncoupling protein 3 gene expression in C(2)C(12) muscle cells.

Publications

Effects of eicosapentaenoic acid and docosahexaenoic acid on uncoupling protein 3 gene expression in C(2)C(12) muscle cells.

Similar Datasets

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