UCP1 deficiency increases susceptibility to diet-induced obesity with age
UCP1 deficiency increases susceptibility to diet-induced obesity with age
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DOI：
10.1111/j.1474-9726.2005.00157.x
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发表时间：
2005-06-01
期刊：
影响因子：
7.8
通讯作者：
Yamashita, H
中科院分区：
文献类型：
--
作者：
Kontani, Y;Wang, Y;Yamashita, H
线粒体解偶联蛋白基因失活导致小鼠（Ucp 1（-/-）小鼠）非颤抖性产热的丧失导致对寒冷的敏感性增加，并在年轻时对饮食诱导的肥胖产生意想不到的抵抗力。为了阐明UCP 1在整个生命过程中体重调节的作用以及UCP 1缺乏对寿命的影响，我们纵向分析了在23 ℃的房间中保持的UCP 1（-/-）小鼠的表型。在标准食物饮食条件下，基因型之间的体重和寿命没有差异，而在高脂（HF）饮食条件下，突变小鼠随着年龄的增长而肥胖。与Ucp 1（+/+）小鼠相比，Ucp 1（-/-）小鼠在3月龄突变体的脂肪组织中显示出与产热和脂肪酸代谢相关的基因表达增加，例如β 3-肾上腺素能受体;然而，在喂食HF饮食的11月龄Ucp 1（-/-）小鼠中，Ucp 1（+/+）小鼠中增加的表达减少。同样地，给予标准饮食的Ucp 1（-/-）小鼠棕色脂肪组织中UCP 3和cAMP依赖性蛋白激酶水平的增加在给予HF饮食的Ucp 1（-/-）小鼠中显著降低，这些动物在其脂肪组织中显示出去甲肾上腺素诱导的脂解受损。这些结果表明，在喂食HF饮食的Ucp 1（-/-）小鼠中，β-肾上腺素能反应性和脂肪酸利用率显著减弱，使它们出现迟发性肥胖。我们的研究结果提供的证据表明，UCP 1是既不是必不可少的体重调节，也不是在标准饮食和正常的住房温度条件下的长寿，但缺乏增加与HF饮食相结合的年龄肥胖的易感性。
Loss of nonshivering thermogenesis in mice by inactivation of the mitochondrial uncoupling protein gene (Ucp1(-/-) mice) causes increased sensitivity to cold and unexpected resistance to diet-induced obesity at a young age. To clarify the role of UCP1 in body weight regulation throughout life and influence of UCP1 deficiency on longevity, we longitudinally analyzed the phenotypes of Ucp1(-/-) mice maintained in a room at 23 degrees C. There was no difference in body weight and lifespan between genotypes under the standard chow diet condition, whereas the mutant mice developed obesity with age under the high-fat (HF) diet condition. Compared with Ucp1(+/+) mice, Ucp1(-/-) mice showed increased expression of genes related to thermogenesis and fatty acid metabolism, such as beta 3-adrenergic receptor, in adipose tissues of the 3-month-old mutants; however, the augmented expression was reduced in Ucp1(+/+) mice in 11-month-old Ucp1(-/-) mice fed the HF diet. Likewise, the increased levels of UCP3 and cAMP-dependent protein kinase in the brown adipose tissue of Ucp1(-/-) mice given the standard diet were decreased significantly in that of Ucp1(-/-) mice fed the HF diet, which animals showed impaired norepinephrine-induced lipolysis in their adipose tissues. These results suggest profound attenuation of beta-adrenergic responsiveness and fatty acid utilization in Ucp1(-/-) mice fed the HF diet, bringing them to late-onset obesity. Our findings provide evidence that UCP1 is neither essential for body weight regulation nor for longevity under conditions of standard diet and normal housing temperature, but deficiency increases susceptibility to obesity with age in combination with HF diet.