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

被引：154

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：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

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.

引用

页数：10

共 42 条

[1] The propeptide mediates formation of stromal stores of PROMIC-1: Role in determining prostate cancer outcome [J].

Bauskin, AR ;

Brown, DA ;

Junankar, S ;

Rasiah, KK ;

Eggleton, S ;

Hunter, M ;

Liu, T ;

Smith, D ;

Kuffner, T ;

Pankhurst, GJ ;

Johnen, H ;

Russell, PJ ;

Barret, W ;

Stricker, PD ;

Grygiel, JJ ;

Kench, JG ;

Henshall, SM ;

Sutherland, RL ;

Breit, SN .

CANCER RESEARCH, 2005, 65 (06) :2330-2336

[2] Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer [J].

Bauskin, Asne R. ;

Brown, David A. ;

Kuffner, Tamara ;

Johnen, Heiko ;

Luo, X. Wei ;

Hunter, Mark ;

Breit, Samuel N. .

CANCER RESEARCH, 2006, 66 (10) :4983-4986

[3] Acutely reduced locomotor activity is a major contributor to Western diet-induced obesity in mice [J].

Bjursell, Mikael ;

Gerdin, Anna-Karin ;

Lelliott, Christopher J. ;

Egecioglu, Emil ;

Elmgren, Anders ;

Tornell, Jan ;

Oscarsson, Jan ;

Bohlooly-Y, Mohammad .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2008, 294 (02) :E251-E260

[4] MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily [J].

Bootcov, MR ;

Bauskin, AR ;

Valenzuela, SM ;

Moore, AG ;

Bansal, M ;

He, XY ;

Zhang, HP ;

Donnellan, M ;

Mahler, S ;

Pryor, K ;

Walsh, BJ ;

Nicholson, RC ;

Fairlie, WD ;

Por, SB ;

Robbins, JM ;

Breit, SN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (21) :11514-11519

[5]

Breit SN, 2011, NEPHROL DIAL TRANSPL

[6] Measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improves prostate cancer diagnosis [J].

Brown, DA ;

Stephan, C ;

Ward, RL ;

Law, M ;

Hunter, M ;

Bauskin, AR ;

Amin, J ;

Jung, K ;

Diamandis, EP ;

Hampton, GM ;

Russell, PJ ;

Giles, GG ;

Breit, SN .

CLINICAL CANCER RESEARCH, 2006, 12 (01) :89-96

[7]

Brown DA, 2003, CLIN CANCER RES, V9, P2642

[8] Antibody-based approach to high-volume genotyping for MIC-1 polymorphism [J].

Brown, DA ;

Bauskin, AR ;

Fairlie, WD ;

Smith, MD ;

Liu, T ;

Xu, N ;

Breit, SN .

BIOTECHNIQUES, 2002, 33 (01) :118-+

[9] Identifying the energy gap: Magnitude and determinants of 5-year weight gain in midage women [J].

Brown, WJ ;

Williams, L ;

Ford, JH ;

Ball, K ;

Dobson, AJ .

OBESITY RESEARCH, 2005, 13 (08) :1431-1441

[10] Macrophage inhibitory cytokine-1 is increased in individuals before type 2 diabetes diagnosis but is not an independent predictor of type 2 diabetes: the Whitehall II study [J].

Carstensen, Maren ;

Herder, Christian ;

Brunner, Eric J. ;

Strassburger, Klaus ;

Tabak, Adam G. ;

Roden, Michael ;

Witte, Daniel R. .

EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2010, 162 (05) :913-917

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