Capric Acid Up-Regulates UCP3 Expression without PDK4 Induction in Mouse C2C12 Myotubes

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  • ABE Tomoki
    Departments of Nutritional Physiology, Tokushima University Graduate School
  • HIRASAKA Katsuya
    Departments of Nutritional Physiology, Tokushima University Graduate School Graduate School of Fisheries Science and Environmental Studies, Nagasaki University
  • KOHNO Shohei
    Departments of Nutritional Physiology, Tokushima University Graduate School Pharmacology/Toxicology, College of Pharmacy, University of Texas
  • TOMIDA Chisato
    Departments of Nutritional Physiology, Tokushima University Graduate School
  • HARUNA Marie
    Departments of Nutritional Physiology, Tokushima University Graduate School
  • UCHIDA Takayuki
    Departments of Nutritional Physiology, Tokushima University Graduate School
  • OHNO Ayako
    Departments of Nutritional Physiology, Tokushima University Graduate School
  • OARADA Motoko
    Medical Mycology Research Center, The University of Chiba
  • TESHIMA-KONDO Shigetada
    Departments of Nutritional Physiology, Tokushima University Graduate School
  • OKUMURA Yuushi
    Departments of Nutritional Physiology, Tokushima University Graduate School Graduate School of Nutritional Sciences, Sagami Women’s University
  • CHOI Inho
    Division of Biological Science and Technology, College of Science and Technology, Yonsei University
  • AOYAMA Toshiaki
    Central Research Laboratory, The Nisshin OilliO Group, Ltd.
  • TERAO Junji
    Food Science, Institute of Biomedical Sciences, Tokushima University Graduate School
  • NIKAWA Takeshi
    Departments of Nutritional Physiology, Tokushima University Graduate School

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Uncoupling protein 3 (UCP3) and pyruvate dehydrogenase kinase 4 (PDK4) in skeletal muscle are key regulators of the glucose and lipid metabolic processes that are involved in insulin resistance. Medium-chain fatty acids (MCFAs) have anti-obesogenic effects in rodents and humans, while long-chain fatty acids (LCFAs) cause increases in body weight and insulin resistance. To clarify the beneficial effects of MCFAs, we examined UCP3 and PDK4 expression in skeletal muscles of mice fed a MCFA- or LCFA-enriched high-fat diet (HFD). Five-week feeding of the LCFA-enriched HFD caused high body weight gain and induced glucose intolerance in mice, compared with those in mice fed the MCFA-enriched HFD. However, the amounts of UCP3 and PDK4 transcripts in the skeletal muscle of mice fed the MCFA- or LCFA-enriched HFD were similar. To further elucidate the specific effects of MCFAs, such as capric acid (C10:0), on lipid metabolism in skeletal muscles, we examined the effects of various FAs on expression of UCP3 and PDK4, in mouse C2C12 myocytes. Although palmitic acid (C16:0) and lauric acid (C12:0) significantly induced expression of both UCP3 and PDK4, capric acid (C10:0) upregulated only UCP3 expression via activation of peroxisome proliferator-activated receptor-δ. Furthermore, palmitic acid (C16:0) disturbed the insulin-induced phosphorylation of Akt, while MCFAs, including lauric (C12:0), capric (C10:0), and caprylic acid (C12:0), did not. These results suggest that capric acid (C10:0) increases the capacity for fatty acid oxidation without inhibiting glycolysis in skeletal muscle.

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