Abstract 15144: Macrophage Migration Inhibitory Factor Knockout Preserves Cardiac Function in High Fat Diet-Induced Metabolic Syndrome
Background: Metabolic syndrome (MetS) is a constellation of multiple metabolic risk factors leading to cardiac anomalies en route to the ultimate heart failure. Animal and clinical studies have suggested that MIF (macrophage migration inhibitory factor) may serve as a primary candidate promoting the development of metabolic syndrome. The aim of the present study was to examine the impact of MIF deficiency on high fat (HF) diet-induced metabolic syndrome as well as cardiac injury and the underlying mechanisms involved.
Methods and Results: Wild type (WT) and MIF knockout (MIF-/-) mice were fed a low fat (LF) diet or HF diet for 20 weeks. HF diet-intake induced MetS (obesity, glucose intolerance, and dyslipidemia) in WT and MIF-/- mice. Whole-animal calorimetry analysis showed that HF diet decreased oxygen consumption, CO2 production, respiratory exchange ratio (RER), and locomotor activity, but increased heart generation in WT and MIF-/- mice. Echocardiography displayed decreased fractional shortening (FS), increased wall thickness, left ventricular end diastolic and systolic diameter (LVEDD, LVESD) in HF diet-fed wild type mice, which were restored by MIF knockout. HF diet impaired cardiomyocyte contractile function by inhibiting peak shortening and maximal velocity, and increasing time-to-90% relengthening, the effect of which was alleviated by MIF deficiency. HF diet resulted in cardiac hypertrophy and interstitial fibrosis accumulation, which were attenuated by MIF deficiency. In addition, immunohistochemical staining and Western blot data indicated that HF diet-induced cardiac injury was associated with increased cardiac inflammation and decreased autophagy activity, the effects of which were restored by MIF knockout.
Conclusions: These results indicate that MIF deficiency failed to prevent HF diet-induced MetS although it preserved cardiac homeostasis, probably through inhibiting cardiac inflammation and restoring cardiac autophagy. Our findings may provide a novel approach for the treatment and prevention of MetS-related cardiac injury.
- © 2013 by American Heart Association, Inc.