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

## TL;DR

Cis-palmitoleic acid (cPOA) helps regulate lipid metabolism in mice by shifting diacylglycerol (DAG) metabolism, offering potential for treating obesity and related diseases.

## Contribution

This study reveals cPOA's dose-dependent regulation of DAG metabolic shunting, providing new insights for precision metabolic interventions.

## Key findings

- Low-dose cPOA reduces hepatic lipid accumulation by inhibiting DAG-to-TAG conversion.
- Medium-to-high doses of cPOA redirect DAG flux toward phospholipid metabolism, lowering body weight and adiposity.
- cPOA modulates gene expression to regulate lipid synthesis and oxidation, with DAG(36:3) as a potential biomarker for metabolic dysregulation.

## 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.