Anethole dithiolethione improves liver fatty acid metabolism in hamster fed high-fat diets

Abstract“Lipotoxicity” induced by excessive accumulation of free fatty acids (FFAs) in the liver, especially saturated FAs and their toxic metabolites, is closely related to metabolic diseases such as nonalcoholic fatty liver disease (NAFLD). Hydrogen sulfide (H2S), a novel gaseous signaling molecule, has been reported to have lipid-lowering effects, but its effect on FAs metabolism remains unclear. The purpose of this study was to investigate the effect and mechanisms of anethole dithiolethione (ADT, a sustained-release H2S donor) on hepatic FAs metabolism. ADT was administered daily for 4 weeks in male Syrian golden hamsters fed a high fat diet (HFD), and FAs profiles of liver tissues were analyzed using GC-MS. The results showed that in HFD-fed hamsters, ADT treatment significantly reduced the accumulation of saturated and monounsaturated fatty acids (C16:0, C18:0, C16:1, and C18:1n9), while increased the content of n-6 and n-3 series polyunsaturated fatty acids (C20:3n6, C20:4n6, and C22:6n3). Mechanistically, ADT obviously inhibited the overexpression of ACC1, FAS and SCD1, and up-regulated the levels of FATPs, L-FABP, CPT1α, FADS1 and FADS2. Notably, ADT evidently induced Mitofusin1 to facilitate mitochondrial fusion and optimize β-oxidation. These findings suggest that ADT plays a beneficial role by regulating the synthesis, desaturation, β-oxidation, uptake, binding/isolation, and transport of FAs. In conclusion, ADT is effective in improving liver FAs metabolic disorders and liver injuries caused by HFD.