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

Research output: Contribution to journalArticlepeer-review

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 statusAccepted/In press - 2021

Keywords

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

ASJC Scopus subject areas

  • Food Science

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