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

• Published in: Food science & nutrition 2021-05, Vol.9 (5), p.2733-2742
• Main Authors: Ko, Chih‐Yuan, Lo, Yangming Martin, Xu, Jian‐Hua, Chang, Wen‐Chang, Huang, Da‐Wei, Wu, James Swi‐Bea, Yang, Cho‐Hua, Huang, Wen‐Chung, Shen, Szu‐Chuan
• Format: Article
• Language: English
• Subjects: Accumulation; alpha‐lipoic acid; Antibodies; Apoptosis; Carnitine; Carnitine palmitoyltransferase; Caspase; Chronic illnesses; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Domains; Fatty acids; Fatty liver; Glucose; High fat diet; Hyperglycemia; Inflammation; Insulin resistance; Interleukins; Kinases; Laboratory animals; Leucine; Lipid peroxidation; Lipids; Lipoic acid; Liver; Liver diseases; NLRP3 inflammasome; nonalcoholic fatty liver disease; Nucleotides; Oral administration; Original Research; Oxidation; Palmitoyltransferase; Plasma; Proteins; Pyrin protein; Rodents; Streptozocin; Triglycerides; type 2 diabetes
• ISSN: 2048-7177; 2048-7177
• DOI: 10.1002/fsn3.2235

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. Alpha‐lipoic acid alleviates hepatic triglyceride accumulation by suppressing the NLRP3 inflammasome pathway, suppressing lipid generation, and promoting lipid oxidation in high‐fat diet and streptozotocin‐induced type 2 diabetic rats.