P2-HNF4α alters linoleic acid metabolism and mitigates soybean oil-induced obesity: role for oxylipins
Abstract
Oxylipins-oxidized metabolites of polyunsaturated fatty acids (PUFAs)-are associated with several pathological conditions. We previously showed that oxylipin metabolites of linoleic acid (LA) and alpha-linolenic acid positively correlate with obesity in wild-type (WT) mice fed a high fat diet (35% kcal fat) based on soybean oil (SO). Here, we compare the effect of the SO diet (10% kcal LA) to an isocaloric diet based on coconut oil (CO) that is low in LA (2% kcal) in HNF4α exon swap male mice that express only the P2 form of HNF4α (α7HMZ). α7HMZ mice gained significantly less weight on the SO diet than WT mice and exhibited neither glucose intolerance nor fatty liver as did the WT mice. Untargeted metabolomics of the liver revealed increased levels of LA and decreased levels of PUFA-derived C18 diols in α7HMZ compared to WT. Proteomics identified decreased levels of several enzymes involved in PUFA metabolism (CYP2Cs, EPHX1, FADS2, ACOX1/2) as the likely cause of decreased diols. Correlation analysis of hepatic oxylipins with body weight, coupled with a 16-weeks treatment with a soluble epoxide inhibitor (sEHI), identified the oxylipins most likely to be potential drivers of obesity as 9,10-DiHOME, 12,13-DiHOME, 9,10-DiHODE and 12,13-DiHODE. Hepatic accumulation of omega-6 and omega-3 oxylipin metabolites of the essential fatty acids, linoleic and alpha-linolenic, are necessary but not sufficient for diet-induced obesity.
Read the paper
Related studies
- eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
- Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
- OptiType: precision HLA typing from next-generation sequencing data
- Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications
- Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
- Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.