Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada.
J Appl Physiol (1985). 2010 Apr;108(4):933-40. doi: 10.1152/japplphysiol.01281.2009. Epub 2010 Feb 4.
Obesity increases the incidence of cardiac arrhythmias and impairs wound healing. However, it is presently unknown whether a high-fat diet affects arrhythmic risk or wound healing before the onset of overt obesity or hyperlipidemia. After 8 wk of feeding a high-fat diet to adult female rats, a nonsignificant increase in body weight was observed and associated with a normal plasma lipid profile. Following ischemia/reperfusion injury, scar length (standard diet 0.29 +/- 0.09 vs. high-fat 0.32 +/- 0.13 cm), thickness (standard diet 0.047 +/- 0.02 vs. high-fat 0.059 +/- 0.01 cm), and collagen alpha(1) type 1 content (standard diet 0.21 +/- 0.04 vs. high-fat 0.20 +/- 0.04 arbitrary units/mm(2)) of infarcted hearts were not altered by the high-fat diet. However, the mortality rate was greatly increased 24 h postinfarction (from 5% to 46%, P < 0.01 for ischemia/reperfusion rats; from 20% to 89%, P < 0.0001, in complete-occlusion rats) in high-fat fed rats, in association with a higher prevalence of ventricular arrhythmias. Ventricular arrhythmia inducibility was also significantly increased in noninfarcted rats fed a high-fat diet. In the hearts of rats fed a high-fat diet, connexin-40 expression was absent, connexin-43 was hypophosphorylated and lateralized, and neurofilament-M immunoreactive fiber density (standard diet 2,020 +/- 260 vs. high-fat diet 2,830 +/- 250 microm(2)/mm(2)) and tyrosine hydroxylase protein expression were increased (P < 0.05). Thus, in the absence of overt obesity and hyperlipidemia, sympathetic hyperinnervation and an aberrant pattern of gap junctional protein expression and regulation in the heart of female rats fed a high-fat diet may have contributed in part to the higher incidence of inducible cardiac arrhythmias.
肥胖增加了心律失常的发生率，并影响了伤口愈合。然而，目前尚不清楚高脂肪饮食是否会在明显肥胖或高脂血症发生之前影响心律失常的风险或伤口愈合。在给成年雌性大鼠喂食高脂肪饮食 8 周后，观察到体重有轻微增加，同时伴随着正常的血浆脂质谱。在缺血/再灌注损伤后，梗死心脏的瘢痕长度（标准饮食 0.29 +/- 0.09 与高脂肪饮食 0.32 +/- 0.13 cm）、厚度（标准饮食 0.047 +/- 0.02 与高脂肪饮食 0.059 +/- 0.01 cm）和胶原α(1)I 型含量（标准饮食 0.21 +/- 0.04 与高脂肪饮食 0.20 +/- 0.04 任意单位/mm(2)）不受高脂肪饮食的影响。然而，高脂肪饮食喂养的大鼠在缺血/再灌注后 24 小时的死亡率大大增加（缺血/再灌注大鼠从 5%增加到 46%，P < 0.01；完全闭塞大鼠从 20%增加到 89%，P < 0.0001），同时室性心律失常的发生率也大大增加。高脂饮食喂养的非梗死大鼠的室性心律失常易感性也显著增加。在喂食高脂肪饮食的大鼠心脏中，连接蛋白 40 表达缺失，连接蛋白 43 去磷酸化并侧向化，神经丝-M 免疫反应性纤维密度（标准饮食 2,020 +/- 260 与高脂肪饮食 2,830 +/- 250 microm(2)/mm(2)）和酪氨酸羟化酶蛋白表达增加（P < 0.05）。因此，在没有明显肥胖和高脂血症的情况下，喂食高脂肪饮食的雌性大鼠心脏中的交感神经过度支配以及缝隙连接蛋白表达和调节的异常模式可能部分导致可诱导性心律失常的发生率增加。
