Ren Jun
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, 1000 E. University Avenue, Dept. 3375, University of Wyoming, Laramie, WY 82071, USA.
Obesity (Silver Spring). 2007 Dec;15(12):2932-41. doi: 10.1038/oby.2007.350.
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.
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.
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.
Our data suggest that high-fat diet and ADH transgene may exaggerate ethanol-induced cardiac depression and protein damage in response to ethanol.
高脂饮食和酒精摄入与肥胖相关，会导致发病率和死亡率增加。本研究旨在探讨高脂饮食与酒精代谢酶乙醇脱氢酶（ADH）在乙醇诱导的心脏抑制中的相互作用。
对喂食低脂肪或高脂肪饮食16周的ADH转基因小鼠和B型友伴病毒（FVB）小鼠的心肌细胞进行机械特性和细胞内钙离子特性测量。通过蛋白质免疫印迹法评估对心脏存活至关重要的两种蛋白质——蛋白激酶B（Akt）和叉头框蛋白O3a（Foxo3a）的表达。通过羰基形成来确定心脏损伤情况。
高脂饮食而非ADH导致肥胖，但无高血糖或高血压，延长了90%再拉伸时间（TR90），降低了峰值缩短率（PS）以及最大缩短/再拉伸速度（±dL/dt），且不影响细胞内钙离子特性。乙醇抑制了低脂喂养的FVB小鼠心肌细胞的PS和细胞内钙离子升高。ADH而非高脂饮食将乙醇诱导的PS和±dL/dt抑制阈值降低至更低水平。在高脂组而非ADH组中，乙醇诱导的心脏抑制幅度更大，且无叠加效应。乙醇分别下调和上调Akt和Foxo3a的表达，并抑制细胞内钙离子升高，而ADH、高脂饮食或两者共同作用会放大这些效应。高脂饮食而非ADH增强了未用乙醇处理小鼠的Foxo3a表达和羰基含量。乙醇刺激显著增强了蛋白质羰基形成，ADH、高脂饮食或两者共同作用会增强这种反应。
我们的数据表明，高脂饮食和ADH转基因可能会加剧乙醇诱导的心脏抑制以及乙醇引起的蛋白质损伤。
