Oleoylethanolamide mitigates cardiac metabolic alterations secondary to obesity induced by high-fat diet in C57/BL6J mice

Abstract Background It is well known that high-fat diet (HFD) feeding causes cardiac inflammation, remodeling, and dysfunction, increased fat intake, especially saturated fat, a major driver of cardiometabolic diseases. Oleoylethanolamide (OEA) member acylethanolamides recognized for its metabolic anti-inflammatory properties due to the high affinity different receptors role as modulator endocannabinoid system. OEA effects on cardiovascular alterations caused by overnutrition are still unknown. Purpose The aim this study was evaluate impact treatment changes induced HFD in obese mice. Methods Male C57Bl/6J mice were divided into 3 groups: control group (STD) receiving standard chow diet; fed with 20 weeks; treated (HFD+OEA 2,5 mg/kg/die i.p.) from week 12 20. Results In mice, reduced body weight measured throughout experimental period. Before sacrifice, we performed oral glucose tolerance test (OGTT), where HFD+OEA showed an improvement insulin sensitivity, altered HFD. led significant increase production inflammatory cytokines chemokines, such interleukin (IL)-1b, IL-6, monocyte chemoattractant protein (MCP)1 pro-fibrotic marker fibrillin tissue. Conversely, normalized transcription above-mentioned pro-inflammatory mediators heart also gene expressions levels fatty acid transporter CD36, significantly HFD-fed have been found be linked myocardial lipid accumulation. We evaluated expression adipokines adiponectin meteorin-like (Metrnl), finding ventricular both OEA. Moreover, induces AMPK AKT phosphorylation, whose pathways converge towards phosphorylation AS160, kinase implicated translocation (GLUT) 4 cardiomyocyte membrane, mechanism involved modulation metabolism. Since it has reported autophagy disorders like obesity, studied effect autophagosome formation, determined LC3II, autophagosomal membrane marker, markedly treatment. Conclusions Taken together, our results indicate potential cardioprotective molecule able reduce gain, ameliorate disposal improving blood glucose, restore related decrease proinflammatory profibrotic markers at level, Funding Acknowledgement Type funding sources: Public Institution(s). Main source(s): Fondo de Investigationes Sanitarias, Instituto Salud Carlos III