(04-02-15) Lowering Body Weight in Obese Mice with Diastolic Heart Failure Improves Cardiac Insulin Sensitivity and Function

(04-02-15) Lowering Body Weight in Obese Mice with Diastolic Heart Failure Improves Cardiac Insulin Sensitivity and Function: Implications for the Obesity Paradox.
Sankaralingam S1, Alrob OA1, Zhang L1, Jaswal JS1, Wagg CS2, Fukushima A1, Padwal RS3, Johnstone DE3, Sharma AM3, Lopaschuk GD4.
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Abstract
Recent studies suggest improved outcomes and survival in obese heart failure patients (i.e. the obesity paradox), although obesity and heart failure unfavourably alters cardiac function and metabolism. We investigated the effects of weight loss on cardiac function and metabolism in obese heart failure mice. Obesity and heart failure were induced by feeding mice a high fat diet (HF, 60% kcal from fat) for 4 wk, following which an abdominal aortic constriction (AAC) was produced. Four wk post-AAC, mice were switched to a low fat diet (12% kcal from fat; HF AAC LF) or maintained on a HF (HF AAC HF) for a further 10 wk. At 18 wk, HF AAC LF mice weighed less than HF AAC HF. Diastolic function was improved in HF AAC LF mice, while cardiac hypertrophy was decreased, and accompanied by decreased SIRT1 expression, increased FOXO1 acetylation, and increased atrogin-1 expression compared to HF AAC HF mice. Insulin stimulated glucose oxidation was increased in hearts from HF AAC LF, compared to HF AAC HF. Thus, lowering body weight by switching to LF diet in obese mice with heart failure is associated with decreased cardiac hypertrophy, and improvements in both cardiac insulin sensitivity and diastolic function, suggesting that weight loss does not negatively impact heart function in the setting of obesity.

Diabetes. 2014 Dec 18. pii: DB_141050. [Epub ahead of print]

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