Alpha-lipoic acid preserves skeletal muscle mass in type 2 diabetic OLETF rats

Oak-Kee Hong; Jang-Won Son; Hyuk-Sang Kwon; Seong-Su Lee; Sung-Rae Kim; Soon Jib Yoo

doi:10.1186/s12986-018-0302-y

Alpha-lipoic acid preserves skeletal muscle mass in type 2 diabetic OLETF rats

Nutr Metab (Lond). 2018 Sep 29:15:66. doi: 10.1186/s12986-018-0302-y. eCollection 2018.

Authors

Oak-Kee Hong¹, Jang-Won Son², Hyuk-Sang Kwon³, Seong-Su Lee², Sung-Rae Kim², Soon Jib Yoo²

Affiliations

¹ 1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222, Banpo-daro, Seocho-gu, Seoul, 06591 Republic of Korea.
² 2Division 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.
³ 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul, 07345 Republic of Korea.

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; Diabetes mellitus; Diabetic rat; Muscle mass; Skeletal muscle.