PPARa-NFkB heterodimer mediates obesity cardiomyopathy through autocrine production of IL-6

This study investigates the molecular mechanism of obesity cardiomyopathy. We found that high-fat diet (HFD) consumption stimulates IL-6 production in cardiomyocytes through the formation of a PPARa/NFkB heterodimer. This local autocrine production of IL-6 is a key driver of diastolic dysfunction in the early stages of obesity. Overall design: ChIP-seq was conducted to identify the genomic binding sites of PPARa, RelA, and p50 in mouse heart tissue. To assess changes in the recruitment of these transcription factors to bona fide PPAR and NF-?B binding elements, we compared mice fed a normal diet (ND) with those fed a high-fat diet (HFD) for one month.