Alpha-lipoic acid preserves skeletal muscle mass in type 2 diabetic OLETF rats
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RESEARCH
Open Access
Alpha-lipoic acid preserves skeletal muscle mass in type 2 diabetic OLETF rats Oak-Kee Hong1, Jang-Won Son2, Hyuk-Sang Kwon3, Seong-Su Lee2, Sung-Rae Kim2 and Soon Jib Yoo2*
Abstract Background: Increased oxidative stress and impaired antioxidant defense are important mechanisms in the pathogenesis of diabetic myopathy. Alpha-lipoic acid (ALA) has been indicated as a weight-loss treatment in rodents and humans, but studies are limited. In the present study, we aimed to determine the influence of ALA, a potent biological antioxidant, on metabolic and growth processes in diabetic rat skeletal muscle. Methods: Male 25-week-old type 2 diabetic rats (OLETF) were randomly divided into two groups, a control group (OLETF-C) and an ALA-treated group (OLETF-ALA) supplemented with 100 mg/kg ALA for 8 weeks. Age-matched, healthy, nondiabetic LETO (LETO-C) rats were used as controls. Results: At 32 weeks of age, body weight was decreased by 6.8%, and the areas under the curve of IP-GTT, fasting glucose, and insulin were less in OLETF-ALA rats compared with OLETF-C rats. ALA significantly preserved muscle mass and enhanced muscle fiber cross-sectional area and fiber frequency percentage in the skeletal muscle of OLETF rats. Although the activation of myoD, myogenin, and myostatin in gastrocnemius muscle was significantly inhibited in OLETF-ALA rats relative to OLETF-C rats, there were no differences in the expression levels of muscle atrogin-1 and MuRF1 between the two groups. ALA treatment significantly increased the levels of phosphorylated 5′-AMPK, SIRT1, and PGC-1α, as well as the levels of phosphorylated AKT, mTOR, and p70S6 kinase in OLETF-ALA rats compared with OLETF-C rats. In contrast, the levels of phosphorylated p38 MAPK, IRS-1, and FOXO1 were decreased in OLETF-ALA rats compared with OLETF-C rats. Conclusions: ALA treatment preserved mass in the gastrocnemius muscles of OLETF rats. ALA significantly upregulated the AMPK/SIRT1/PGC-1α and AKT/mTOR/p70S6K signaling pathways in OLETF rat skeletal muscle. Therefore, ALA may be a potential therapeutic intervention for skeletal muscle loss in animal models of insulin resistance. Keywords: Alpha-lipoic acid, Diabetic rat, Diabetes mellitus, Skeletal muscle, Muscle mass
Background Skeletal muscle is the most abundant tissue in the vertebrate body, and one of the most dynamic and plastic tissues in the human body [1]. In humans, skeletal muscle comprises approximately 40% of total body weight and contains 50–75% of all body proteins [1]. The maintenance of skeletal muscle mass plays an important role in disease prevention and quality of life [2–5]. Muscle mass, which can change quite rapidly, is the result of a * Correspondence: [email protected]; [email protected] 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 327, Sosa-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14647, Republic of Korea Full list of author information is available at the end
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