Acute high fat diet promotes NF‐κB activation and cardioprotection through circulating adiponectin (652.1)

Abstract

Prolonged high fat diet (HFD) consumption leads to diverse pathologies such as obesity, type II diabetes, atherosclerosis, and myocardial infarction. Paradoxically, studies have shown that short term HFD is cardioprotective against myocardial ischemia and reperfusion (I/R). This response is NF‐κB dependent, a hallmark of preconditioning pathways. This study will address the hypothesis that the adipose‐derived circulating cytokine, adiponectin promotes the activation of NF‐κB in an acute HFD by acting on cardiac receptors and stimulating cardioprotective gene programs.To investigate this in an intact in vivo AdipoQ KO model, infarct size formed in 24h HFD and ctrl chow fed mice were compared. In vitro studies employed HL‐1 cells treated with adipocyte conditioned or ctrl medium to assess a direct response of adiponectin on cardiomyocytes after undergoing a simulated I/R (sim I/R) event in a hypoxic chamber. Cell death was measured by lactate dehydrogenase assay and NF‐κB activation was indirectly measured through the activation downstream NF‐κB ‐dependent genes (VEGF, HIF1a) by qRT‐PCR.Results showed no significant difference in infarct size between the HFD and ctrl chow AdKO mice suggesting the loss of HFD cardioprotection due to loss of adiponectin. Furthermore, treatment in conditioned medium demonstrated significantly reduced cell death and upregulation of NF‐κB‐dependent gene programs after sim I/R in comparison to untreated cells. Our data supports adiponectin as a crucial molecular activator in acute HFD cardioprotection.