GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

被引：355

作者：

Patel, Satish ^{[1
]}

Alvarez-Guaita, Anna ^{[1
]}

Melvin, Audrey ^{[1
]}

Rimmington, Debra ^{[1
]}

Dattilo, Alessia ^{[1
]}

Miedzybrodzka, Emily L. ^{[1
]}

Cimino, Irene ^{[1
]}

Maurin, Anne-Catherine ^{[3
]}

Roberts, Geoffrey P. ^{[1
]}

Meek, Claire L. ^{[1
]}

Virtue, Samuel ^{[1
]}

Sparks, Lauren M. ^{[6
]}

Parsons, Stephanie A. ^{[6
]}

Redman, Leanne M. ^{[7
]}

Bray, George A. ^{[7
]}

Liou, Alice P. ^{[4
]}

Woods, Rachel M. ^{[5
]}

Parry, Sion A. ^{[5
,11
]}

Jeppesen, Per B. ^{[8
]}

Kolnes, Anders J. ^{[9
]}

Harding, Heather P. ^{[1
,2
]}

Ron, David ^{[1
,2
]}

Vidal-Puig, Antonio ^{[1
]}

Reimann, Frank ^{[1
]}

Gribble, Fiona M. ^{[1
]}

Hulston, Carl J. ^{[5
]}

Farooqi, I. Sadaf ^{[1
]}

Fafournoux, Pierre ^{[3
]}

Smith, Steven R. ^{[6
]}

Jensen, Jorgen ^{[10
]}

Breen, Danna ^{[4
]}

Wu, Zhidan ^{[4
]}

Zhang, Bei B. ^{[4
]}

Coll, Anthony P. ^{[1
]}

Savage, David B. ^{[1
]}

O'Rahilly, Stephen ^{[1
]}

机构：

[1] Univ Cambridge, Inst Metab Sci, Med Res Council, Metab Res Labs,Wellcome Trust, Cambridge CB2 0QQ, England

[2] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England

[3] Univ Clermont Auvergne, Unite Nutr Humaine, INRA, F-63000 Clermont Ferrand, France

[4] Pfizer Global R&D, Internal Med Res Unit, 1 Portland St, Cambridge, MA USA

[5] Loughborough Univ, Sch Sport Exercise & Hlth Sci, Loughborough LE11 3TU, Leics, England

[6] Florida Hosp, Translat Res Inst Metab & Diabet, Orlando, FL USA

[7] Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA

[8] Aarhus Univ, Aarhus Univ Hosp, Dept Clin Med, Aarhus, Denmark

[9] Natl Hosp Norway, Oslo Univ Hosp, Dept Endocrinol, Sect Specialized Endocrinol, Oslo, Norway

[10] Norwegian Sch Sport Sci, Dept Phys Performance, Oslo, Norway

[11] Univ Oxford, Metab Res Grp, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford OX3 7LE, England

来源：

CELL METABOLISM | 2019年 / 29卷 / 03期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

DIFFERENTIATION FACTOR 15; TGF-BETA SUPERFAMILY; MACROPHAGE INHIBITORY CYTOKINE-1; UNFOLDED PROTEIN RESPONSE; ENERGY-EXPENDITURE; INSULIN-RESISTANCE; ADIPOSE-TISSUE; ER STRESS; TRANSLATIONAL REGULATION; LIPID-METABOLISM;

D O I：

10.1016/j.cmet.2018.12.016

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.

引用

页码：707 / +

页数：20

共 74 条

[1] PLAB induction in fenretinide-induced apoptosis of ovarian cancer cells occurs via a ROS-dependent mechanism involving ER stress and JNK activation [J].