Abstract
Excessive liver lipid deposition is a vital risk factor for the development of many diseases. Here, we fed Sprague-Dawley rats with a control or α-lipoic acid-supplemented diet (0.2%) for 5 weeks to elucidate the effects of α-lipoic acid on preventive ability, hepatic lipid metabolism-related gene expression, and the involved regulatory mechanisms. In the current study, α-lipoic acid supplementation lowered plasma triglyceride level and hepatic triglyceride content. Reduced hepatic lipid deposition was closely associated with inhibiting fatty acid-binding protein 1 and fatty acid synthase expression, as well as increasing phosphorylated hormone-sensitive lipase expression at the protein level in α-lipoic acid-exposed rats. Hepatic miRNA sequencing revealed increased expression of miR-3548 targeting the 3′untranslated region of Fasn mRNA, and the direct regulatory link between miRNA-3548 and FASN was verified by dual-luciferase reporter assay. Taken together, α-lipoic acid lowered hepatic lipid accumulation, which involved changes in miRNA-mediated lipogenic genes.
Highlights
Excessive deposition of hepatic triglycerides has been associated with obesity [1], diabetes [2], hyperglycemia [3], and insulin resistance [4]
Hepatic lipid deposition is tightly controlled by key enzymes, including stearoylCoA desaturase (SCD), sterol acetyl CoA carboxylase (ACC), fatty acid synthase (FASN), carnitine palmitoyltransferase 1α (CPT1α), adipose triglyceride lipase (ATGL), hormonesensitive lipase (HSL), cluster of differentiation 36 (CD36), and fatty acid-binding protein 1 (FABP1), which participate in the uptake, synthesis, transportation, and oxidation of fatty acids [11]
ACC, FASN, and SCD are responsible for lipogenesis [12,13], and ATGL, HSL, and CPT1α are key factors in lipolysis, while CD36 and FABP1 facilitate cellular uptake and intracellular trafficking of fatty acids [14]
Summary
Excessive deposition of hepatic triglycerides has been associated with obesity [1], diabetes [2], hyperglycemia [3], and insulin resistance [4]. Liver-specific knockout of CD36 or ACC1 reduces hepatic fat accumulation [15,16], while over-expression of CD36 increases hepatic fatty acid uptake and lipid deposition in vivo and in vitro [17]. Α-Lipoic acid exerts various pharmacological activities for treating chronic diseases, such as Alzheimer’s disease, Down’s syndrome, diabetes mellitus, cognitive dysfunction, hypertension, and some cancers [23,24,25]. It has anti-platelet activity and regulates muscle energy metabolism as well as other functions [26,27]. The present study was performed to examine the changes in hepatic lipid metabolism-genes and proteins, as well as the expression of miRNAs targeting lipogenic genes in rats treated with α-lipoic acid, which will provide further insight into the lipidlowering effect induced by α-lipoic acid
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