Abstract 20128: Adiponectin Upregulation in Epicardial Fat Ameliorates Ischemia- Induced Cardiac Dysfunction in Obese Rats Through Recruitment of LKB1 and pAMPK.
High Fat (HF) diets increase cardiovascular risk presumably by a decrease in the redox state, radical scavenging activities and decreased adiponectin release in epicardial fat. Adiponectin plays a fundamental role in vascular protection, energy homeostasis and increases LKB1 and AMPK for maintenance of the redox state. Induction of heme oxygenase-1 (HO-1) may increase epicardial adiponectin, thereby providing cardio protection via the recruitment of LKB1 and AMPK and a restoration of the redox homeostasis.
Aim: To determine the effect of cardiovascular fat on heart function and whether upregulation of antioxidant genes in visceral fat affects the response of the heart to ischemia.
Method: Sprague Dawley rats were fed normal chow or HF diet for 26 weeks. An inducer of HO-1, cobalt protoporphyrin (CoPP), 3mg/Kg was injected (S.C.) weekly for 26 weeks. LV fibrosis (histomorphometry) and coronary resistance in isolated hearts during development of ischemia, epicardial fat adiponectin, insulin resistance, and redox state genes including HO-1 and Thioredoxin reductase-1 (TxR1) levels were measured.
Results: HF diets decreased LV evP, dp/dt max (p<0.01) while increasing CR (p<0.01) and perivascular and myocardial fibrosis (p<0.05). Increased in HO-1 decreased adiposity and insulin resistance (p<0.05) resulted in increased fat and cardiac tissue adiponectin and HO-1 levels (p<0.05). These were associated with increased tissue phosphorylation of LKB1, AMPK and ACC. The increase in phosphorylation of AMPK was accompanied by an increase in redox state genes, including HO-1 and TxR1. Conversely, inhibitors of HO activity reversed all these beneficial effects.
Conclusion: Increases in HO-1 and TxR1 restored the redox state by increases in radical scavenging activities. The decrease in redox stress was associated with increases in adiponectin and pAMPK resulted in the amelioration of cardiac dysfunction under ischemic conditions. We could not exclude that the decrease in adiposity and insulin resistance may have contributed to this cardioprotection. However, HO-1 -adiponectin-mediated increase in radical scavenging activities suggests that they have a potential therapeutic target in the prevention of HF mediated cardiodysfunction.
- © 2010 by American Heart Association, Inc.