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Papers of the Week

2022 Mar 25

Am J Physiol Heart Circ Physiol

Metabolic Transformation of Fat in Obesity Determines the Inflammation Resolving Capacity of Splenocardiac and Cardiorenal Networks in Heart Failure.



All fats are not created equal, and despite the extensive literature, the effect of fat intake is the most debated question in obesity, cardiovascular, and cardiorenal research. Cellular and molecular mechanisms underlying cardiac dysfunction and consequent heart failure in the setting of obesity are not well understood. Our understanding of how fats are metabolically transformed after non-reperfused myocardial infarction (MI), in particular, is incomplete. Here, using male C57BL/6J mice (2 months old), we determined the role of omega-6 fatty acids (provided as safflower oil, SO, for 12 weeks) followed by supplementation with docosahexaenoic acid (DHA; n-3 fatty acids) for 8 weeks prior to MI. With SO feeding, inflammation resolution was impaired. Specialized pro-resolving mediators (SPMs) increased in DHA fed-mice to reverse the effects of SO, while prostaglandins and thromboxane B2 reduced in the spleen and amplified multiple resolving mechanisms in heart and kidney post-MI. DHA amplified the number of resolving macrophages and cardiac reparative pathways of the splenocardiac and cardiorenal networks in acute heart failure, with higher T cellsin chronic heart failure with marked expression of Foxp3 in the myocardium. Our findings indicate that surplus ingestion of SO intensified systemic, baseline, non-resolving inflammation, and DHA intake dominates splenocardiac resolving phase with the biosynthesis of SPMs and controlled cardiorenal inflammation in heart failure survivor mice.