Wenwen Huang, Bei Gao, Longxiang Liu, Qi Song, Mengru Wei, Hongzhen Li, Chunlong Sun, Wang Li, Wen Du, Jinjun Shan
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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.
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:
manuscripts regarding research proposals and research ideas will be particularly welcomed
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
we also accept manuscripts communicating to a broader audience with regard to research projects financed with public funds