Novel Effect of <i>p</i>-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets

<i>p</i>-coumaric acid (<i>p</i>-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...

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Main Authors: Zhiyi Yuan, Xi Lu, Fan Lei, Hong Sun, Jingfei Jiang, Dongming Xing, Lijun Du
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/28/12/4641
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author Zhiyi Yuan
Xi Lu
Fan Lei
Hong Sun
Jingfei Jiang
Dongming Xing
Lijun Du
author_facet Zhiyi Yuan
Xi Lu
Fan Lei
Hong Sun
Jingfei Jiang
Dongming Xing
Lijun Du
author_sort Zhiyi Yuan
collection DOAJ
description <i>p</i>-coumaric acid (<i>p</i>-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 <i>p</i>-CA on the down-regulation of accumulated lipids in vivo and in vitro. <i>p</i>-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, <i>p</i>-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, <i>p</i>-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, <i>p</i>-CA is capable of regulating lipid metabolism and is a potential therapeutic drug or health care product for hyperlipidemia and fatty liver.
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spelling doaj.art-9b76b2d4931644ba8e18a92131285e382023-11-18T11:48:21ZengMDPI AGMolecules1420-30492023-06-012812464110.3390/molecules28124641Novel Effect of <i>p</i>-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-DropletsZhiyi Yuan0Xi Lu1Fan Lei2Hong Sun3Jingfei Jiang4Dongming Xing5Lijun Du6College of Pharmacy, Chongqing Medical University, Chongqing 400016, ChinaSchool of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, ChinaSchool of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, ChinaInstitute of Medicinal Plant and Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100094, ChinaSchool of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, ChinaSchool of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, ChinaSchool of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China<i>p</i>-coumaric acid (<i>p</i>-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 <i>p</i>-CA on the down-regulation of accumulated lipids in vivo and in vitro. <i>p</i>-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, <i>p</i>-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, <i>p</i>-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, <i>p</i>-CA is capable of regulating lipid metabolism and is a potential therapeutic drug or health care product for hyperlipidemia and fatty liver.https://www.mdpi.com/1420-3049/28/12/4641<i>p</i>-coumaric acidhepatic lipaselipid dropletNAFLDPPAR
spellingShingle Zhiyi Yuan
Xi Lu
Fan Lei
Hong Sun
Jingfei Jiang
Dongming Xing
Lijun Du
Novel Effect of <i>p</i>-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets
Molecules
<i>p</i>-coumaric acid
hepatic lipase
lipid droplet
NAFLD
PPAR
title Novel Effect of <i>p</i>-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets
title_full Novel Effect of <i>p</i>-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets
title_fullStr Novel Effect of <i>p</i>-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets
title_full_unstemmed Novel Effect of <i>p</i>-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets
title_short Novel Effect of <i>p</i>-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets
title_sort novel effect of i p i coumaric acid on hepatic lipolysis inhibition of hepatic lipid droplets
topic <i>p</i>-coumaric acid
hepatic lipase
lipid droplet
NAFLD
PPAR
url https://www.mdpi.com/1420-3049/28/12/4641
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