Novel Effect of p-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets
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Published:2023-06-08
Issue:12
Volume:28
Page:4641
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Yuan Zhiyi1, Lu Xi2, Lei Fan2, Sun Hong3, Jiang Jingfei2, Xing Dongming2, Du Lijun2
Affiliation:
1. College of Pharmacy, Chongqing Medical University, Chongqing 400016, China 2. School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China 3. Institute of Medicinal Plant and Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100094, China
Abstract
p-coumaric acid (p-CA), a common plant phenolic acid with multiple bioactivities, has a lipid-lowering effect. As a dietary polyphenol, its low toxicity, with the advantages of prophylactic and long-term administration, makes it a potential drug for prophylaxis and the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which it regulates lipid metabolism is still unclear. In this study, we studied the effect of p-CA on the down-regulation of accumulated lipids in vivo and in vitro. p-CA increased a number of lipase expressions, including hormone-sensitive lipase (HSL), monoacylglycerol lipase (MGL) and hepatic triglyceride lipase (HTGL), as well as the expression of genes related to fatty acid oxidation, including long-chain fatty acyl-CoA synthetase 1 (ACSL1), carnitine palmitoyltransferase-1 (CPT1), by activating peroxisome proliferator-activated receptor α, and γ (PPARα and γ). Furthermore, p-CA promoted adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and enhanced the expression of the mammalian suppressor of Sec4 (MSS4), a critical protein that can inhibit lipid droplet growth. Thus, p-CA can decrease lipid accumulation and inhibit lipid droplet fusion, which are correlated with the enhancement of liver lipases and genes related to fatty acid oxidation as an activator of PPARs. Therefore, p-CA is capable of regulating lipid metabolism and is a potential therapeutic drug or health care product for hyperlipidemia and fatty liver.
Funder
National S&T Major Special Project for New Drug R&D Program of China National Natural Science Foundation of China Youth Fund of National Natural Science Foundation, China Chongqing Special Foundation for Postdoctoral Research Proposal, China Program for Youth Innovation in Future Medicine, Chongqing Medical University, China
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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