The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases

Vicky W.W. Tsai; Yasmin Husaini; Amanda Sainsbury; David A. Brown; Samuel N. Breit

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The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases

机译：能量稳态中的MIC-1 / GDF15-GFRAL途径：对肥胖，恶病症和其他相关疾病的影响

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MIC-1/GDF15 is a stress response cytokine and a distant member of the transforming growth factor beta (TGFb) superfamily, with no close relatives. It acts via a recently identified receptor called glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL), which is a distant orphan member of the GDNF receptor family that signals through the tyrosine kinase receptor Ret. MIC-1/GDF15 expression and serum levels rise in response to many stimuli that initiate cell stress and as part of a wide variety of disease processes, most prominently cancer and cardiovascular disease. The best documented actions of MIC-1/GDF15 are on regulation of energy homeostasis. When MIC-1/GDF15 serum levels are substantially elevated in diseases like cancer, it subverts a physiological pathway of appetite regulation to induce an anorexia/cachexia syndrome initiated by its actions on hindbrain neurons. These effects make it a potential target for the treatment of both obesity and anorexia/cachexia syndromes, disorders lacking any highly effective, readily accessible therapies.

机译：MIC-1 / GDF15是应力响应细胞因子和转化生长因子β（TGFB）超家族的远端构件，没有近亲。它通过最近鉴定的受体起作用称为神经源性神经营养因子（GDNF）受体α样（GFRAL）的受体，其是GDNF受体系列的远离孤儿构件，其通过酪氨酸激酶受体RET信号。 MIC-1 / GDF15表达和血清水平响应许多引发细胞应激的刺激，并且作为各种疾病过程的一部分，最突出的癌症和心血管疾病。 MIC-1 / GDF15的最佳记录动作是对能量稳态的调节。当MIC-1 / GDF15血清水平在癌症等疾病中显着升高时，它颠覆食欲调节的生理途径，以诱导由其对后脑神经元的作用发起的厌食/恶病症综合征。这些效果使其成为治疗肥胖症和厌食/恶病症综合征的潜在目标，缺乏任何高效，易于访问的疗法的疾病。

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来源
《Cell metabolism》 |2018年第3期|共16页
作者
Vicky W.W. Tsai; Yasmin Husaini; Amanda Sainsbury; David A. Brown; Samuel N. Breit;
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作者单位

St Vincent’s Centre for Applied Medical Research St Vincent’s Hospital;

St Vincent’s Centre for Applied Medical Research St Vincent’s Hospital;

The University of Sydney The Boden Institute of Obesity Nutrition Exercise &

Eating Disorders;

St Vincent’s Centre for Applied Medical Research St Vincent’s Hospital;

St Vincent’s Centre for Applied Medical Research St Vincent’s Hospital;

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原文格式 PDF
正文语种 eng
中图分类内分泌腺疾病及代谢病;
关键词
MIC-1/GDF15; GFRAL; GDNF; TGFb; obesity; cachexia; cancer; inflammation; area postrema; nucleus of the solitary tract;

机译：MIC-1 / GDF15;GFRAL;GFRAL;GDNF;TGFB;肥胖症;恶病毒;癌症;炎症;区域POSTREMA;孤独的泌尿束核心;

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专利

1. The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases [J] . Vicky W.W. Tsai, Yasmin Husaini, Amanda Sainsbury, Cell metabolism . 2018,第3期

机译：能量稳态中的MIC-1 / GDF15-GFRAL途径：对肥胖，恶病症和其他相关疾病的影响
2. Energy homeostasis and cachexia in chronic kidney disease. [J] . Mak RH, Cheung W Pediatric nephrology: journal of the International Pediatric Nephrology Association . 2006,第12期

机译：慢性肾脏疾病中的能量稳态和恶病质。
3. Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention [J] . Anna Kopczak, Christian L. Roth, G#xFC, Journal of Clinical Medicine . 2015,第9期

机译：颅咽管瘤患者的下丘脑肥胖：与下丘脑损伤程度有关的能量稳态紊乱及其对肥胖症干预的意义
4. Early Nutrition as a Major Determinant of 'Immune Health': Implications for Allergy, Obesity and Other Noncommunicable Diseases [C] . Susan L Prescott Nestlé Nutrition Institute Workshop . 2016

机译：早期营养作为“免疫健康”的主要决定因素：对过敏，肥胖和其他非传染性疾病的影响
5. Effects of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, Synthetic Peptide Leptin Mimetics, on Energy Balance and Glucose Homeostasis in Diet-Induced Obese (DIO) Mice [D] . Wang, Anke. 2020

机译：[D-Leu-4] -Ob3和MA-[D-Leu-4] -Ob3，合成肽瘦蛋白模拟物，在饮食诱导的肥胖（DIO）小鼠中的能量平衡和葡萄糖稳态上的影响
6. Integrative Aspects of Energy Homeostasis and Metabolic Diseases: Isolated duodenal exclusion increases energy expenditure and improves glucose homeostasis in diet-induced obese rats [O] . Rodrigo Muñoz, Jill S. Carmody, Nicholas Stylopoulos, -1

机译：能量稳态和代谢性疾病的综合方面：孤立的十二指肠排斥增加了饮食诱发的肥胖大鼠的能量消耗并改善了葡萄糖稳态。
7. The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases [O] . Vicky W.W. Tsai, Yasmin Husaini, Amanda Sainsbury, 2018

机译：能量稳态中的MIC-1 / GDF15-GFRAL途径：对肥胖，恶病症和其他相关疾病的影响

The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases

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