Division of Gastroenterology and Hepatology, Univ. of Missouri, Columbia, MO 65212, USA.
Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G874-83. doi: 10.1152/ajpgi.00510.2010. Epub 2011 Feb 24.
The maintenance of normal body weight either through dietary modification or being habitually more physically active is associated with reduced incidence of nonalcoholic fatty liver disease (NAFLD). However, the means by which weight gain is prevented and potential mechanisms activated remain largely unstudied. Here, we sought to determine the effects of obesity prevention by daily exercise vs. caloric restriction on NAFLD in the hyperphagic, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. At 4 wk of age, male OLETF rats (n = 7-8/group) were randomized to groups of ad libitum fed, sedentary (OLETF-SED), voluntary wheel running exercise (OLETF-EX), or caloric restriction (OLETF-CR; 70% of SED) until 40 wk of age. Nonhyperphagic, control strain Long-Evans Tokushima Otsuka (LETO) rats were kept in sedentary cage conditions for the duration of the study (LETO-SED). Both daily exercise and caloric restriction prevented obesity and the development of type 2 diabetes observed in the OLETF-SED rats, with glucose tolerance during a glucose tolerance test improved to a greater extent in the OLETF-EX animals (30-50% lower glucose and insulin areas under the curve, P < 0.05). Both daily exercise and caloric restriction also prevented excess hepatic triglyceride and diacylglycerol accumulation (P < 0.001), hepatocyte ballooning and nuclear displacement, and the increased perivenular fibrosis and collagen deposition that occurred in the obese OLETF-SED animals. However, despite similar hepatic phenotypes, OLETF-EX rats also exhibited increased hepatic mitochondrial fatty acid oxidation, enhanced oxidative enzyme function and protein content, and further suppression of hepatic de novo lipogenesis proteins compared with OLETF-CR. Prevention of obesity by either daily exercise or caloric restriction attenuates NAFLD development in OLETF rats. However, daily exercise may offer additional health benefits on glucose homeostasis and hepatic mitochondrial function compared with restricted diet alone.
通过饮食调整或习惯性增加身体活动来维持正常体重与降低非酒精性脂肪性肝病（NAFLD）的发病率有关。然而，预防体重增加和潜在机制激活的方法在很大程度上仍未得到研究。在这里，我们试图确定通过日常运动与热量限制预防肥胖对高脂饮食诱导的肥胖性非酒精性脂肪肝病大鼠（OLETF 大鼠）的影响。在 4 周龄时，雄性 OLETF 大鼠（n = 7-8/组）被随机分为自由进食、久坐（OLETF-SED）、自愿轮跑运动（OLETF-EX）或热量限制（OLETF-CR；SED 的 70%）组，直到 40 周龄。非肥胖对照品系长野 Tokushima Otsuka（LETO）大鼠在整个研究期间保持在久坐笼中（LETO-SED）。每日运动和热量限制均能预防 OLETF-SED 大鼠肥胖和 2 型糖尿病的发生，葡萄糖耐量试验期间，OLETF-EX 动物的葡萄糖耐量得到了更大程度的改善（血糖和胰岛素曲线下面积降低 30-50%，P < 0.05）。每日运动和热量限制也能预防肝内甘油三酯和二酰基甘油的过度积累（P < 0.001）、肝细胞气球样变和核移位，以及肥胖 OLETF-SED 大鼠发生的肝周纤维化和胶原沉积增加。然而，尽管肝脏表型相似，OLETF-EX 大鼠的肝线粒体脂肪酸氧化增加，氧化酶功能和蛋白含量增强，并且肝内从头合成脂肪生成蛋白的表达进一步受到抑制，与 OLETF-CR 相比。无论是通过日常运动还是热量限制来预防肥胖都可以减轻 OLETF 大鼠的 NAFLD 发展。然而，与单纯饮食限制相比，日常运动可能对葡萄糖稳态和肝线粒体功能有额外的健康益处。
