Morris R Tyler, Laye Matthew J, Lees Simon J, Rector R Scott, Thyfault John P, Booth Frank W
Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, 1600 E. Rollins, Columbia, MO 65201, USA.
J Appl Physiol (1985). 2008 Mar;104(3):708-15. doi: 10.1152/japplphysiol.01034.2007. Epub 2007 Dec 13.
The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a model of hyperphagic obesity in which the animals retain the desire to run voluntarily. Running wheels were provided for 4-wk-old OLETF rats for 16 wk before they were killed 5 h (WL5), 53 h (WL53), or 173 h (WL173) after the wheels were locked. Sedentary (SED) OLETF rats that were not given access to running wheels served as age-matched cohorts. Epididymal fat pad mass, adipocyte volume, and adipocyte number were 58%, 39%, and 47% less, respectively, in WL5 than SED rats. Contrary to cessation of daily running in Fischer 344 x Brown Norway rats, epididymal fat did not increase during the first 173 h of running cessation in the OLETF runners. Serum insulin and glucose levels were 77% and 29% less, respectively, in WL5 than SED rats. Oil red O staining for intramyocellular lipid accumulation was not statistically different among groups. However, lipid peroxidation levels, as determined by total trans-4-hydroxy-2-nonenal (4-HNE) and 4-HNE normalized to oil red O, was higher in epitrochlearis muscles of SED than WL5, WL53, and WL173 rats. mRNA levels of glutathione S-transferase-alpha type 4, an enzyme involved in cellular defense against electrophilic compounds such as 4-HNE, were higher in epitrochlearis muscle of WL53 than WL173 and SED rats. In contrast, 4-HNE levels in omental fat were unaltered. Epitrochlearis muscle palmitate oxidation and relative transcript levels for peroxisome proliferator-activated receptor-delta and peroxisome proliferator-activated receptor-gamma coactivator type 1 were surprisingly not different between runners and SED rats. In summary, voluntary running was associated with lower levels of lipid peroxidation in skeletal muscle without significant changes in intramyocellular lipids or mitochondrial markers in OLETF rats at 20 wk of age. Therefore, even in a genetic animal model of extreme overeating, daily physical activity promotes improved health of skeletal muscle.
大冢长-艾氏德岛肥胖（OLETF）大鼠是一种食欲亢进性肥胖模型，该模型中的动物仍有自主跑步的欲望。在4周龄的OLETF大鼠被处死前的16周内，为它们提供跑步轮，处死时间分别为跑步轮锁定后的5小时（WL5）、53小时（WL53）或173小时（WL173）。未接触跑步轮的久坐不动（SED）OLETF大鼠作为年龄匹配的对照组。与SED大鼠相比，WL5大鼠的附睾脂肪垫质量、脂肪细胞体积和脂肪细胞数量分别减少了58%、39%和47%。与Fischer 344×Brown Norway大鼠停止每日跑步不同，OLETF跑步大鼠在停止跑步的前173小时内附睾脂肪并未增加。与SED大鼠相比，WL5大鼠的血清胰岛素和葡萄糖水平分别降低了77%和29%。各组间肌内脂质积累的油红O染色无统计学差异。然而，通过总反式-4-羟基-2-壬烯醛（4-HNE）以及4-HNE与油红O标准化后测定的脂质过氧化水平，SED大鼠肱桡肌中的高于WL5、WL53和WL173大鼠。谷胱甘肽S-转移酶α4型（一种参与细胞对抗诸如4-HNE等亲电化合物防御的酶）的mRNA水平，在WL53大鼠的肱桡肌中高于WL173大鼠和SED大鼠。相比之下，网膜脂肪中的4-HNE水平未改变。令人惊讶的是，跑步大鼠和SED大鼠的肱桡肌棕榈酸氧化以及过氧化物酶体增殖物激活受体δ和过氧化物酶体增殖物激活受体γ共激活因子1型的相对转录水平并无差异。总之，在20周龄的OLETF大鼠中，自主跑步与骨骼肌中较低的脂质过氧化水平相关，而肌内脂质或线粒体标志物无显著变化。因此，即使在极度暴饮暴食的遗传动物模型中，日常体育活动也能促进骨骼肌健康状况的改善。
