TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator

被引：150
|
作者：
Tsai, Vicky Wang-Wei [1 ,2 ]
Macia, Laurence [3 ]
Johnen, Heiko [1 ,2 ]
Kuffner, Tamara [1 ,2 ]
Manadhar, Rakesh [1 ,2 ]
Jorgensen, Sebastian Beck [4 ]
Lee-Ng, Ka Ki Michelle [1 ,2 ]
Zhang, Hong Ping [1 ,2 ]
Wu, Liyun [1 ,2 ]
Marquis, Christopher Peter [5 ]
Jiang, Lele [1 ,2 ]
Husaini, Yasmin [1 ,2 ]
Lin, Shu [3 ]
Herzog, Herbert [3 ]
Brown, David A. [1 ,2 ]
Sainsbury, Amanda [3 ]
Breit, Samuel N. [1 ,2 ]
机构：
[1] St Vincents Hosp, St Vincents Ctr Appl Med Res, Sydney, NSW 2010, Australia
[2] Univ New S Wales, Sydney, NSW, Australia
[3] Garvan Inst Med Res, Neurosci Program, Sydney, NSW, Australia
[4] Novo Nordisk AS, Diabet Res Unit, Malov, Denmark
[5] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia
来源：
PLOS ONE | 2013年 / 8卷 / 02期
基金：
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词：
MACROPHAGE INHIBITORY CYTOKINE-1; GROWTH-DIFFERENTIATION FACTOR-15; BONE MORPHOGENETIC PROTEIN-7; FACTOR-BETA SUPERFAMILY; DIET-INDUCED OBESITY; BROWN ADIPOGENESIS; SERUM; MIC-1; INDIVIDUALS; DIAGNOSIS;
D O I：
10.1371/journal.pone.0055174
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1(-/-)) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1(-/-) mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1(-/-) mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.
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页数：10
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