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A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload

¹Cardiac Ultrasound Laboratory, Cardiology Division, Department of Medicine, and ²Anesthesia Center for Critical Care Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital, ³Department of Radiology, Massachusetts General Hospital and Harvard Medical School, ⁴Cardiovascular Research Center, Massachusetts General Hospital, and ⁵Shriners Hospitals for Children and Harvard Medical School, Boston, Massachusetts; ⁶Institut National de la Santé et de la Recherche Médicale, U870, IFR62, Oullins; and ⁷Institut National de la Santé et de la Recherche Médicale E 0226, Universite Claude Bernard Lyon I, Lyon, France

Submitted 8 February 2008 ; accepted in final form 27 October 2008

Insulin resistance is an increasingly prevalent condition in humans that frequently clusters with disorders characterized by left ventricular (LV) pressure overload, such as systemic hypertension. To investigate the impact of insulin resistance on LV remodeling and functional response to pressure overload, C57BL6 male mice were fed a high-fat (HFD) or a standard diet (SD) for 9 days and then underwent transverse aortic constriction (TAC). LV size and function were assessed in SD- and HFD-fed mice using serial echocardiography before and 7, 21, and 28 days after TAC. Serial echocardiography was also performed on nonoperated SD- and HFD-fed mice over a period of 6 wk. LV perfusion was assessed before and 7 and 28 days after TAC. Nine days of HFD induced systemic and myocardial insulin resistance (assessed by myocardial ¹⁸F-fluorodeoxyglucose uptake), and myocardial perfusion response to acetylcholine was impaired. High-fat feeding for 28 days did not change LV size and function in nonbanded mice; however, TAC induced greater hypertrophy, more marked LV systolic and diastolic dysfunction, and decreased survival in HFD-fed compared with SD-fed mice. Compared with SD-fed mice, myocardial perfusion reserve was decreased 7 days after TAC, and capillary density was decreased 28 days after TAC in HFD-fed mice. A short duration of HFD induces insulin resistance in mice. These metabolic changes are accompanied by increased LV remodeling and dysfunction after TAC, highlighting the impact of insulin resistance in the development of pressure-overload-induced heart failure.

heart failure; myocardial perfusion

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				D. J. Chess, R. J. Khairallah, K. M. O'Shea, W. Xu, and W. C. Stanley A high-fat diet increases adiposity but maintains mitochondrial oxidative enzymes without affecting development of heart failure with pressure overload Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1585 - H1593. [Abstract] [Full Text] [PDF]