Food preservative sorbic acid deregulates hepatic fatty acid
metabolism
Chia-Hui Chen a,1, Sin-Ni Ho b,1, Po-An Hu a,1, Yu Ru Kou b, Tzong-Shyuan Lee a,*
a Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
b Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Sorbic acid (SA) is one of the most commonly used food preservatives worldwide. Despite SA having no hepatotoxicity at legal dosages, its effect on hepatic lipid metabolism is still unclear. We investigated the effect of SA on hepatic lipid metabolism and its mechanism of action in C57BL/6 mice. Daily treatment with SA (1 g/kg in diet) for 4 weeks did not alter the body weight, organ weight, and blood lipids in mice. However, hepatic lipid accumulation, particularly that of triglycerides, fatty acids, and glycerol, but not cholesteryl ester and free cholesterol, was increased with SA treatment. Mechanistically, SA decreased the expression of proteins related to de novo fatty acid lipogenesis, fatty acid internalization, and very low-density lipoprotein (VLDL) secretion-related pathways, including sterol regulatory elementbinding proteins, acetyl-coA carboxylase, fatty acid synthase, liver fatty acid-binding protein, CD36, and apolipoprotein E. In contrast, SA increased the expression of diacylglycerol O-acyltransferase 2, the key enzyme for triacylglycerol synthesis. Moreover, SA downregulated the protein expression of autophagy-related and b-oxidation-related pathways, the two major metabolic pathways for lipid metabolism, including LC-3, beclin-1, autophagy related protein 5 (ATG-5) and ATG-7, acyl-CoA synthetase long chain family member 1, carnitine palmitoyltransferase Ia, peroxisome proliferator- activated receptor a (PPARa), PPARg, and PPARg coactivator-1. Collectively, SA deregulates de novo lipogenesis and fatty acid internalization, VLDL secretion, autophagy, and b-oxidation in the liver, leading to impaired lipid clearance and ultimately, resulting in lipid accumulation in the liver.
Keywords: Autophagy, b-oxidation, Fatty acid metabolism, Liver, Sorbic acid
https://doi.org/10.38212/2224-6614.1055
(https://www.jfda-online.com/journal/vol28/iss2/2/)