Abstract 2946: The Obesity Paradox: Insights Into Mechanisms of Cardioprotection in Obesity in Leptin Deficient Mice With Cardiac Pressure Overload
Background: The “obesity paradox” refers to observations that obese individuals are more likely to get heart disease than normal weight subjects, but have better survival once diagnosed with heart disease. The improved outcomes in obesity could be due to better nutritional reserve, however, mechanisms are difficult to investigate in humans.
Methods: Leptin deficient (ob/ob) mice and lean, wild type (WT) mice underwent transverse aortic banding (TAB) at 6 weeks of age—when ob/ob are obese (~ double nl body weight) and insulin resistant but nondiabetic. Cardiac function was assessed by echocardiography and left ventricular (LV) catheterization. Capillary density was assessed by lectin staining and fibrosis was measured with picrosirius red staining. Angiogenic and profibrotic cytokines were measured in cardiac tissue, serum and para-aortic fat.
Results: TAB produced comparable increases in LV pressure and heart weight in ob/ob and WT mice (Table⇓). Despite this, ob/ob mice had much better survival than WT mice. ob/ob TAB mice also had better LV function than WT TAB mice as measured by echocardi-ography or catheterization. Capillary density and myocardial VEGF expression were lower in ob/ob TAB excluding this as a mechanism of better function. Myocardial fibrosis was lower in ob/ob TAB than WT TAB. Serum TGFb was lower in ob/ob TAB than WT TAB, although cardiac expression of TGFb was unchanged. Serum MCP1 was increased in ob/ob mice and para-aortic fat produced more MIP1a and IL6 in obese than WT mice.
Conclusions: Obese mice show evidence of the obesity paradox consisting of improved survival and better cardiac function after aortic banding. This may be related to lower myocardial fibrosis. Production of inflammatory and monocyte attractant cytokines is increased in paravascular fat, but not in heart of obese mice. These findings raise the intriguing possibility that the inflammatory milieu in obesity could lead to improved cardiac healing during acute injury or overload.