<i>Cis</i>-Palmitoleic Acid Regulates Lipid Metabolism via Diacylglycerol Metabolic Shunting

<i>Cis</i>-Palmitoleic Acid Regulates Lipid Metabolism via Diacylglycerol Metabolic Shunting

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...

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Main Authors: Wenwen Huang, Bei Gao, Longxiang Liu, Qi Song, Mengru Wei, Hongzhen Li, Chunlong Sun, Wang Li, Wen Du, Jinjun Shan
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Foods
Subjects:
<i>cis</i>-palmitoleic acid (<i>c</i>POA)
diacylglycerol (DAG) shunting
obesity
metabolic reprogramming
phospholipid synthesis
Online Access:https://www.mdpi.com/2304-8158/14/14/2504
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Summary: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.
ISSN:2304-8158

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