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.