Macrophage Migration Inhibitory Factor (MIF) Knockout Preserves Cardiac Homeostasis through Alleviating Akt- Mediated Myocardial Autophagy Suppression in High Fat Diet-

Background—Macrophage migration inhibitory factor (MIF) plays a role in the development of obesity and diabetes. However, whether MIF plays a role in fat diet-induced obesity and associated cardiac anomalies still remains unknown. The aim of this study was to examine the impact of MIF knockout on high fat diet-induced obesity, obesity-associated cardiac anomalies and the underlying mechanisms involved with a focus on Akt-mediated autophagy. Methods—Adult male wild-type (WT) and MIF knockout (MIF−/−) mice were placed on 45% high fat diet for 5 months. Oxygen consumption, CO2 production, respiratory exchange ratio (RER), locomotor activity, and heat generation were measured using energy calorimeter. Echocardiographic, cardiomyocyte mechanical and intracellular Ca2+ properties were assessed. Apoptosis was examined using TUNEL staining and western blot analysis. Akt signaling pathway and autophagy markers were evaluated. Cardiomyocytes isolated from WT and MIF−/ − mice were treated with recombinant mouse MIF (rmMIF). Results—High fat diet feeding elicited increased body weight gain, insulin resistance, and caloric disturbance in WT and MIF−/ − mice. High fat diet induced unfavorable geometric