Cis-Palmitoleic Acid Regulates Lipid Metabolism via Diacylglycerol Metabolic Shunting.

IF 5.1 2区 农林科学 Q1 FOOD SCIENCE & TECHNOLOGY
Foods Pub Date : 2025-07-17 DOI:10.3390/foods14142504
Wenwen Huang, Bei Gao, Longxiang Liu, Qi Song, Mengru Wei, Hongzhen Li, Chunlong Sun, Wang Li, Wen Du, Jinjun Shan
{"title":"<i>Cis</i>-Palmitoleic Acid Regulates Lipid Metabolism via Diacylglycerol Metabolic Shunting.","authors":"Wenwen Huang, Bei Gao, Longxiang Liu, Qi Song, Mengru Wei, Hongzhen Li, Chunlong Sun, Wang Li, Wen Du, Jinjun Shan","doi":"10.3390/foods14142504","DOIUrl":null,"url":null,"abstract":"<p><p>Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although <i>cis</i>-palmitoleic acid (<i>c</i>POA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of <i>c</i>POA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose <i>c</i>POA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150-300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, <i>c</i>POA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that <i>c</i>POA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1-18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated <i>c</i>POA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases.</p>","PeriodicalId":12386,"journal":{"name":"Foods","volume":"14 14","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Foods","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.3390/foods14142504","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of cPOA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose cPOA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150-300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, cPOA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that cPOA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1-18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated cPOA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases.

顺式棕榈油酸通过二酰基甘油代谢分流调节脂质代谢。
肥胖及相关代谢紊乱与脂质代谢失调密切相关,其中二酰基甘油(DAG)的代谢平衡起着关键作用。虽然顺式棕榈油酸(cPOA)具有抗肥胖作用,但其功效因饮食条件而异,其分子机制尚不清楚。在这项研究中,我们通过脂质组学、途径分析和基因/蛋白表达分析,研究了cPOA对db/db小鼠DAG代谢分流的剂量依赖性调节作用。在基础饲粮中,低剂量cPOA (75 mg/kg)抑制DAG到甘油三酯(TAG)的转化,减少肝脏脂质积累,而中至高剂量(150-300 mg/kg)将DAG的流量转向磷脂代谢途径(如磷脂酰胆碱[PC]和磷脂酰乙醇胺[PE]),显著降低体重和肥胖指数。在高脂饮食(HFD)喂养的小鼠中,cPOA没有减轻体重,但通过抑制dag到tag的转化和重塑磷脂代谢(如抑制pe到pc的转化),减轻了HFD引起的肝脏病理损伤。遗传和蛋白质分析显示,cPOA下调脂肪生成基因(SREBP-1c, SCD-1, FAS)和上调脂肪酸β-氧化酶(CPT1A, ACOX1),同时剂量依赖性地调节DGAT1, CHPT1和PEMT的表达,以驱动DAG代谢分流。值得注意的是,DAG(36:3, 18:1-18:2)是hfd加重代谢失调的潜在生物标志物。本研究阐明了cPOA作为脂质合成和氧化的双向调节剂,通过剂量依赖性的DAG代谢重编程改善脂质稳态。这些发现为肥胖及相关代谢疾病的精确干预提供了新的见解和策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Foods
Foods Immunology and Microbiology-Microbiology
CiteScore
7.40
自引率
15.40%
发文量
3516
审稿时长
15.83 days
期刊介绍: Foods (ISSN 2304-8158) is an international, peer-reviewed scientific open access journal which provides an advanced forum for studies related to all aspects of food research. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists, researchers, and other food professionals to publish their experimental and theoretical results in as much detail as possible or share their knowledge with as much readers unlimitedly as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. There are, in addition, unique features of this journal: Ÿ manuscripts regarding research proposals and research ideas will be particularly welcomed Ÿ electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material Ÿ we also accept manuscripts communicating to a broader audience with regard to research projects financed with public funds
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信