Original Article

Alpha-lipoic acid attenuates insulin resistance and improves glucose metabolism in high fat diet-fed mice

Authors: Yi Yang, Wang Li, Yang Liu, Yan Li, Ling Gao, Jia-jun Zhao
DOI: 10.1038/aps.2014.64


Yi YANG1, 2, *, Wang LI3, Yang LIU3, Yan LI3, Ling GAO4, Jia-jun ZHAO1, 5, *
1Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Ji-nan 250021, China; 2Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China; 3Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China; 4Central Lab Provincial Hospital Affiliated to Shandong University, Ji-nan 250021, China; 5Institute of Endocrinology, Shandong Academy of Clinical Medicine, Ji-nan 250021, China

Aim: To investigate whether alpha-lipoic acid (ALA) could attenuate the insulin resistance and metabolic disorders in high fat diet-fed mice.
Methods: Male mice were fed a high fat diet (HFD) plus ALA (100 and 200 mg·kg-1·d-1) or HFD plus a positive control drug metformin (300 mg·kg-1·d-1) for 24 weeks. During the treatments, the relevant physiological and metabolic parameters of the mice were measured. After the mice were euthanized, blood samples and livers were collected. The expression of proteins and genes related to glucose metabolism in livers were analyzed by immunoblotting and real time-PCR.

Results: HFD induced non-alcoholic fatty liver disease (NAFLD) and abnormal physiological and metabolic parameters in the mice, which were dose-dependently attenuated by ALA. ALA also significantly reduced HFD-induced hyperglycemia and insulin resistance in HFD-fed mice. Furthermore, ALA significantly upregulated the glycolytic enzymes GCK, HK-1 and PK, and the glycogen synthesis enzyme GS, and downregulated the gluconeogenic enzymes PEPCK and G6Pase, thus decreased glucose production, and promoted glycogen synthesis and glucose utilization in livers. Moreover, ALA markedly increased PKB/Akt and GSK3β phosphorylation, and nuclear carbohydrate response element binding protein (ChREBP) expression in livers. Metformin produced similar effects as ALA in HFD-fed mice.

Conclusion: ALA is able to sustain glucose homeostasis and prevent the development of NAFLD in HFD-fed mice.

Keywords: alpha-lipoic acid; metformin; high fat diet; glucose metabolism; insulin resistance; hyperglycemia; non-alcoholic fatty liver disease; hepatic steatosis

This study was supported by the National Natural Science Foundation of China (No 81160103).
* To whom correspondence should be addressed.
E-mail jjzhao@medmail.com.cn (Jia-jun ZHAO); yangyi73422@163.com (Yi YANG)
Received 2014-02-11 Accepted 2014-06-06

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