J Obes Metab Syndr.
2024 Jun;33(2):177-188. 10.7570/jomes23048.
Alpha-Lipoic Acid Induces Adipose Tissue Browning through AMP-Activated Protein Kinase Signaling in Vivo and in Vitro
- Affiliations
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- 1Department of Pharmacy, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
- 2Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan, Taiwan
- 3Department of Nursing, Tzu Chi University of Science and Technology, Hualien, Taiwan
- 4Department of Nursing, Hung Kuang University, Taichung, Taiwan
- 5Department of Pharmacology and Graduate Institute of Pharmacology, National Defense Medical Center, Taipei, Taiwan
- 6Department of Physiology & Biophysics, National Defense Medical Center, Taipei, Taiwan
- KMID: 2557468
- DOI: http://doi.org/10.7570/jomes23048
Abstract
- Background
AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms.
Methods
Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study.
Results
Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects.
Conclusion
ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.
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