Metabolic transformation of fat in obesity determines the inflammation resolving capacity of splenocardiac and cardiorenal networks in heart failure

Ganesh V. Halade, Vasundhara Kain, Xavier De La Rosa, Merry L. Lindsey

Research output: Contribution to journalArticlepeer-review

Abstract

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 nonreperfused myocardial infarction (MI), in particular, is incomplete. Here, using male C57BL/6J mice (2 mo old), we determined the role of omega-6 fatty acids, provided as safflower oil (SO) for 12 wk, followed by supplementation with docosahexaenoic acid (DHA; n-3 fatty acids) for 8 wk before MI. With SO feeding, inflammation resolution was impaired. Specialized proresolving mediators (SPMs) increased in DHA-fed mice to reverse the effects of SO, whereas prostaglandins and thromboxane B2 were 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 Treg cells in chronic heart failure and marked expression of Foxp3þ in the myocardium. Our findings indicate that surplus ingestion of SO intensified systemic, baseline, nonresolving inflammation, and DHA intake dominates splenocardiac resolving phase with the biosynthesis of SPMs and controlled cardiorenal inflammation in heart failure survivor mice.

Original languageEnglish (US)
Pages (from-to)H953-H970
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume322
Issue number6
DOIs
StatePublished - Jun 2022

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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