12-hydroxy-5-8-10-14-17-eicospentaenoic-acid and Obesity

Obesity drives an imbalanced signature of specialized pro-resolving mediators (SPM). Herein, we investigated if high fat diet-induced obesity dysregulates the concentration of SPM intermediates in the brains of C57BL/6 J mice. Furthermore, given the benefits of EPA for cardiometabolic diseases, major depression, and cognition, we probed the effect of an EPA supplemented high fat diet on brain SPM intermediates. Mass spectrometry revealed no effect of the high fat diet on PUFA-derived brain metabolites. EPA also did not have an effect on most brain PUFA-derived metabolites except an increase of 12-hydroxyeicosapentaenoic acid (12-HEPE). In contrast, EPA dramatically increased serum HEPEs and lowered several PUFA-derived metabolites. Finally, untargeted mass spectrometry showed no effects of the high fat diet, with or without EPA, on the brain metabolome. Collectively, these results show the murine brain resists a deficiency in SPM pathway markers in response to a high fat diet and that EPA supplementation increases 12-HEPE levels.

Topics: Animals; Brain Chemistry; Diet, High-Fat; Disease Models, Animal; Eicosapentaenoic Acid; Lipoxins; Male; Mass Spectrometry; Metabolic Networks and Pathways; Metabolomics; Mice; Mice, Obese; Obesity

Cardiovascular disease, a major cause of mortality and morbidity, exhibits sexual dimorphism since the onset of cardiovascular disease occurs later in women than in men. The loss of cardioprotection in older women may be due to an increase in arterial stiffness after menopause. Free fatty acid metabolites of polyunsaturated fatty acids, called oxylipins, are known to impact vessel function and may be responsible for the vascular benefits of polyunsaturated fatty acids. The objectives of this study were to compare the plasma oxylipin profiles of young females (20-55 years), older females (55. Higher 12-lipoxygenase oxylipin plasma concentrations associated with lower arterial stiffness in premenopausal females may be an important contributing factor to sex differences in cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01661543, NCT01562171, NCT01890330, NCT02571114 and NCT02317588.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Adult; Age Factors; Aged; Ankle Brachial Index; Biomarkers; Cardiovascular Diseases; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; Health Status Disparities; Heart Disease Risk Factors; Humans; Male; Menopause; Middle Aged; Obesity; Oxylipins; Pulse Wave Analysis; Risk Assessment; Sex Factors; Up-Regulation; Vascular Stiffness; Young Adult

Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.

Topics: Animals; Atherosclerosis; Cell Differentiation; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Eicosapentaenoic Acid; Foam Cells; Humans; Linseed Oil; Male; Mice; Obesity; PPAR gamma; Soybean Oil; Weight Gain