Dual lipolytic control of body fat storage and mobilization in Drosophila.
Dual lipolytic control of body fat storage and mobilization in Drosophila.
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DOI：
10.1371/journal.pbio.0050137
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发表时间：
2007-06
期刊：
影响因子：
9.8
通讯作者：
Kühnlein RP
中科院分区：
文献类型：
--
作者：
Grönke S;Müller G;Hirsch J;Fellert S;Andreou A;Haase T;Jäckle H;Kühnlein RP
能量稳态是动物生命的基本属性，在脂肪储存和动员之间提供遗传固定的平衡。身体脂肪调节的重要性通过导致人类肥胖和脂肪代谢障碍的功能障碍而被强调。储存脂肪在细胞内脂滴中的包装以及指导储存脂肪动员的各种分子和机制在哺乳动物和昆虫之间是保守的。我们产生了一个果蝇突变体缺乏受体（AKHR）的脂肪动力激素信号通路，昆虫脂解途径相关的β-肾上腺素能信号在哺乳动物。结合遗传、生理和生化分析提供了体内证据，证明AKHR对于储存脂肪的慢性积累和急性动员与哺乳动物脂肪甘油三酯脂肪酶（ATGL）的同系物布鲁默脂肪酶一样重要。同时失去Brummer和AKHR会导致极度肥胖，并阻止果蝇的急性储存脂肪动员。我们的数据表明，储存脂肪的动员在苍蝇是协调两个脂肪分解代谢系统，这是必不可少的，以调整正常的身体脂肪含量，并确保终身脂肪储存的稳态。动物体内储存的脂肪量是其生存的关键参数。虽然脂肪储存不足会在饥荒期间产生风险，但过度储存也会损害健康-人类肥胖与严重的健康威胁有关，如心血管疾病，II型糖尿病和癌症。两个对立过程之间的微妙平衡调节身体脂肪储存：脂肪生成产生脂肪储存，脂肪分解动员脂肪。然而，目前尚不清楚有多少调节系统协调动物的脂解，这些系统是否在进化上是保守的，以及在何种程度上受损的脂解调节导致过量的体脂积累。我们表明，在果蝇果蝇，脂解是双重控制下。两种控制途径中的任何一种失活都会产生脂肪积累过多和脂肪动员能力有限的果蝇。然而，突变果蝇同时缺乏两个脂解系统的关键基因，即使在完全缺乏食物的情况下，它们也极度肥胖，并且在体内脂肪动员方面完全受阻。有趣的是，我们的研究揭示了脂解的关键成分和调节机制在昆虫和哺乳动物之间是进化保守的，这使得果蝇成为研究脂质代谢的有价值的模型系统。同时损失受体的脂肪运动激素和布鲁默甘油三酯脂肪酶会导致极端肥胖，并阻止急性储存脂肪动员苍蝇。
Energy homeostasis is a fundamental property of animal life, providing a genetically fixed balance between fat storage and mobilization. The importance of body fat regulation is emphasized by dysfunctions resulting in obesity and lipodystrophy in humans. Packaging of storage fat in intracellular lipid droplets, and the various molecules and mechanisms guiding storage-fat mobilization, are conserved between mammals and insects. We generated a Drosophila mutant lacking the receptor (AKHR) of the adipokinetic hormone signaling pathway, an insect lipolytic pathway related to ß-adrenergic signaling in mammals. Combined genetic, physiological, and biochemical analyses provide in vivo evidence that AKHR is as important for chronic accumulation and acute mobilization of storage fat as is the Brummer lipase, the homolog of mammalian adipose triglyceride lipase (ATGL). Simultaneous loss of Brummer and AKHR causes extreme obesity and blocks acute storage-fat mobilization in flies. Our data demonstrate that storage-fat mobilization in the fly is coordinated by two lipocatabolic systems, which are essential to adjust normal body fat content and ensure lifelong fat-storage homeostasis. The amount of body fat that an animal stores is a critical parameter for its survival. Although under-storage of fat creates risk during periods of famine, over-storage also impairs fitness—obesity in humans is associated with severe health threats, such as cardiovascular disease, type II diabetes, and cancer. A delicate balance between two antagonistic processes adjusts body fat storage: lipogenesis produces fat stores, and lipolysis mobilizes fat. It is unclear, however, how many regulatory systems orchestrate lipolysis in animals, whether these systems are evolutionarily conserved, and to what extent impaired lipolytic regulation contributes to excessive body fat accumulation. We show that in the fruit fly Drosophila, lipolysis is under dual control. Inactivation of either of the two control pathways generates flies with excessive fat accumulation and limited fat-mobilization capability. Mutant flies simultaneously lacking key genes of both lipolytic systems, however, are extremely obese and completely blocked in body fat mobilization even when fully food deprived. Interestingly, our study reveals that key components and regulatory mechanisms of lipolysis are evolutionarily conserved between insects and mammals, making the fruit fly a valuable model system for research on lipid metabolism. Simultaneous loss of the receptor for adipokinetic hormone and the Brummer triglyceride lipase causes extreme obesity and blocks acute storage fat mobilization in flies.
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影响因子：
9.8
作者：
Lefevre, C;Jobard, F;Fischer, J
通讯作者：
Fischer, J
影响因子：
4.8
作者：
Kurat, CF;Natter, K;Kohlwein, SD
通讯作者：
Kohlwein, SD
DOI：
10.1016/0005-2760(86)90286-9
发表时间：
1986-04-15
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FREDRIKSON, G;TORNQVIST, H;BELFRAGE, P
通讯作者：
BELFRAGE, P
DOI：
10.1006/bbrc.1998.9230
发表时间：
1998-08-28
影响因子：
3.1
作者：
Hauser, F;Sondergaard, L;Grimmelikhuijzen, CJP
通讯作者：
Grimmelikhuijzen, CJP
影响因子：
56.9
作者：
Haemmerle, G;Lass, A;Zechner, R
通讯作者：
Zechner, R