Interaction Between High-Fat Diet and Alcohol Dehydrogenase on Ethanol-Elicited Cardiac Depression in Murine Myocytes

Authors

  • Jun Ren

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    1. Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming
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Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, 1000 E. University Avenue, Dept. 3375, University of Wyoming, Laramie, WY 82071. E-mail: jren@uwyo.edu

Abstract

Objective: Consumption of high-fat diet and alcohol is associated with obesity, leading to enhanced morbidity and mortality. This study was designed to examine the interaction between high-fat diet and the alcohol metabolizing enzyme alcohol dehydrogenase (ADH) on ethanol-induced cardiac depression.

Research Methods and Procedures: Mechanical and intracellular Ca2+ properties were measured in cardiomyocytes from ADH transgenic and Friend Virus-B type (FVB) mice fed a low- or high-fat diet for 16 weeks. Expression of protein kinase B (Akt) and Foxo3a, two proteins essential for cardiac survival, was evaluated by Western blot. Cardiac damage was determined by carbonyl formation.

Results: High fat but not ADH induced obesity without hyperglycemia or hypertension, prolonged time-to-90% relengthening (TR90), and depressed peak shortening (PS) and maximal velocity of shortening/relengthening (± dL/dt) without affecting intracellular Ca2+ properties. Ethanol suppressed PS and intracellular Ca2+ rise in low-fat-fed FVB mouse cardiomyocytes. ADH but not high-fat diet shifted the threshold of ethanol-induced inhibition of PS and ± dL/dt to lower levels. The amplitude of ethanol-induced cardiac depression was greater in the high-fat but not the ADH group without additive effects. Ethanol down- and up-regulated Akt and Foxo3a expression, respectively, and depressed intracellular Ca2+ rise, the effects of which were exaggerated by ADH, high-fat, or both. High-fat diet, but not ADH, enhanced Foxo3a expression and carbonyl content in non-ethanol-treated mice. Ethanol challenge significantly enhanced protein carbonyl formation, with the response being augmented by ADH, high-fat, or both.

Discussion: Our data suggest that high-fat diet and ADH transgene may exaggerate ethanol-induced cardiac depression and protein damage in response to ethanol.

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