Alpha-lipoic acid alleviates NAFLD and triglyceride accumulation in liver via modulating hepatic NLRP3 inflammasome activation pathway in type 2 diabetic rats

Chih Yuan Ko, Yangming Martin Lo, Jian Hua Xu, Wen Chang Chang, Da Wei Huang, James Swi Bea Wu, Cho Hua Yang, Wen Chung Huang, Szu Chuan Shen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The occurrence of nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes mellitus (T2DM). The activation of nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing 3 (NLRP3) inflammasome in the liver may lead to hepatic fat accumulation. Alpha-lipoic acid (ALA) has been reported to improve IR in a T2DM rodent model. We investigated the effects of ALA on NLRP3 inflammasome activation and fat accumulation in the liver of a high-fat diet (HFD) plus streptozotocin (STZ)-induced T2DM rats. The HFD/STZ-induced T2DM rats were orally administered ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. The results showed that the liver triglyceride contents of T2DM rats were 11.35 ± 1.84%, whereas the administration of 50, 100, and 200 mg/kg BW ALA significantly reduced the liver triglyceride contents of T2DM rats to 4.14 ± 0.59%, 4.02 ± 0.41%, and 3.01 ± 1.07%, respectively. Moreover, 200 mg/kg BW ALA significantly decreased the hepatic levels of NLRP3 inflammasome activation-related proteins NLRP3, caspase-1, and interleukin-1β expression by 40.0%, 60.1%, and 24.5%, respectively, in T2DM rats. Furthermore, the expression levels of hepatic fat synthesis-related proteins decreased, namely a 45.4% decrease in sterol regulatory element-binding protein-1c, whereas the expression of hepatic lipid oxidation-related proteins increased, including a 27.5% increase in carnitine palmitoyltransferase, in T2DM rats after 200 mg/kg BW ALA treatment. We concluded that ALA treatment may suppress hepatic NLRP3 inflammasome activation, consequently alleviating NAFLD and excess hepatic lipid accumulation in HFD/STZ-induced T2DM rats.

Original languageEnglish
Pages (from-to)2733-2742
Number of pages10
JournalFood Science and Nutrition
Volume9
Issue number5
DOIs
Publication statusPublished - 2021 May

Keywords

  • NLRP3 inflammasome
  • alpha-lipoic acid
  • nonalcoholic fatty liver disease
  • type 2 diabetes

ASJC Scopus subject areas

  • Food Science

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