Open AccessAlpha‐lipoic acid alleviates NAFLD and triglyceride accumulation in liver via modulating hepatic NLRP3 inflammasome activation pathway in type 2 diabetic rats
Author(s) -
Ko ChihYuan,
Lo Yangming Martin,
Xu JianHua,
Chang WenChang,
Huang DaWei,
Wu James SwiBea,
Yang ChoHua,
Huang WenChung,
Shen SzuChuan
Publication year - 2021
Publication title -
food science and nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.614
H-Index - 27
ISSN - 2048-7177
DOI - 10.1002/fsn3.2235
Subject(s) - inflammasome , endocrinology , medicine , triglyceride , chemistry , nonalcoholic fatty liver disease , streptozotocin , steatosis , fatty liver , diabetes mellitus , inflammation , cholesterol , disease
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.