Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat

Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat
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DOI:
10.1152/japplphysiol.01034.2007
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发表时间:
2008-03-01
影响因子:
3.3
通讯作者:
Booth, Frank W.
Booth, Frank W.
中科院分区:
医学2区
文献类型:
--
作者:
Morris, R. Tyler;Laye, Matthew J.;Booth, Frank W.

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大冢Long-Evans德岛脂肪(OLETF)大鼠是一种过度吞噬性肥胖模型,其中动物保持自主奔跑的欲望。为4周龄OLETF大鼠提供转轮16周,然后在转轮锁定后5 h(WL 5)、53 h(WL 53)或173 h(WL 173)处死。不允许使用跑步轮的久坐(SED)OLETF大鼠作为年龄匹配的队列。附睾脂肪垫质量,脂肪细胞体积和脂肪细胞数量分别为58%,39%和47%,在WL 5比SED大鼠。相反,停止每天运行的Fischer 344 X布朗挪威大鼠,附睾脂肪没有增加,在第一个173小时的运行停止在OLETF运行。血清胰岛素和葡萄糖水平分别为77%和29%,在WL 5比SED大鼠。油红O染色显示肌细胞内脂质蓄积在各组间无统计学差异。然而,脂质过氧化水平,总反式-4-羟基-2-壬烯醛(4-HNE)和4-HNE油红O标准化,测定SED的上滑车肌高于WL 5,WL 53,和WL 173大鼠。谷胱甘肽S-转移酶-α 4型,一种参与细胞防御亲电化合物,如4-HNE的酶,在WL 53的滑车上肌的mRNA水平高于WL 173和SED大鼠。相反,网膜脂肪中的4-HNE水平不变。上滑车肌棕榈酸氧化和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型的相对转录水平在跑步者和SED大鼠之间令人惊讶地没有差异。总之,自愿运行与较低水平的脂质过氧化作用在骨骼肌没有显着变化的肌内脂质或线粒体标记物在20周龄的OLETF大鼠。因此,即使在极端暴饮暴食的遗传动物模型中,日常体力活动也能促进骨骼肌的健康。
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.