Reduced expression of mitochondrial frataxin in mice exacerbates diet-induced obesity
Reduced expression of mitochondrial frataxin in mice exacerbates diet-induced obesity
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DOI：
10.1073/pnas.0611631104
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发表时间：
2007-04-10
影响因子：
11.1
通讯作者：
Ristow, Michael
中科院分区：
文献类型：
--
作者：
Pomplun, Doreen;Voigt, Anja;Ristow, Michael
已发表的证据表明，人类肥胖可能与能量消耗受损有关，原因尚未得到广泛解决。我们产生了氧化磷酸化（OXPHOS）全身性损伤的小鼠，这是由于aP2 crec介导的靶向破坏，以及线粒体frataxin蛋白表达的意外普遍降低。只有当这些动物保持类似西方饮食习惯的高热量饮食时，它们才会积累额外的身体脂肪，导致体重增加，并患上糖尿病，尽管事实上它们的卡路里摄入量和身体活动与对照动物相同。这种表型是由轻微但显著的总能量消耗减少引起的，同时增加了ATP柠檬酸裂解酶的表达，ATP柠檬酸裂解酶是脂肪酸和甘油三酯从头合成的限速步骤。综上所述，这些发现表明，线粒体内氧化代谢的有限损伤直接导致哺乳动物体重过度增加。
Published evidence suggests that adiposity in humans may be linked to impaired energy expenditure for reasons widely unresolved. We have generated mice with a systemic impairment of oxidative phosphorylation (OXPHOS) due to aP2 cre-mediated targeted disruption, and unexpectedly ubiquitous reduction of mitochondrial frataxin protein expression. Only when maintained on a high-calorie diet resembling Westernized eating habits, these animals accumulate additional body fat, leading to increased body mass, and develop diabetes mellitus, despite the fact that both calorie uptake and physical activity were identical to that in control animals. This phenotype is caused by a mild but significant reduction in total energy expenditure paralleled by increased expression of ATP citrate lyase, a rate-limiting step in de novo synthesis of fatty acids and triglycerides. Taken together, these findings indicate that a limited impairment in oxidative metabolism within the mitochondria directly predisposes mammals to excessive body weight gain.