Universität zu Köln

Dodd, Garron T., Andrews, Zane B. ORCID: 0000-0002-9097-7944, Simonds, Stephanie E., Michael, Natalie J., DeVeer, Michael, Bruening, Jens C., Spanswick, David ORCID: 0000-0002-8129-8173, Cowley, Michael A. and Tiganis, Tony ORCID: 0000-0002-8065-9942 (2017). A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding. Cell Metab., 26 (2). S. 375 - 401. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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Abstract

Beige adipocytes can interconvert between white and brown-like states and switch between energy storage versus expenditure. Here we report that beige adipocyte plasticity is important for feeding-associated changes in energy expenditure and is coordinated by the hypothalamus and the phosphatase TCPTP. A fasting-induced and glucocorticoid-mediated induction of TCPTP, inhibited insulin signaling in AgRP/NPY neurons, repressed the browning of white fat and decreased energy expenditure. Conversely feeding reduced hypothalamic TCPTP, to increase AgRP/NPY neuronal insulin signaling, white adipose tissue browning and energy expenditure. The feeding-induced repression of hypothalamic TCPTP was defective in obesity. Mice lacking TCPTP in AgRP/NPY neurons were resistant to diet-induced obesity and had increased beige fat activity and energy expenditure. The deletion of hypothalamic TCPTP in obesity restored feeding-induced browning and increased energy expenditure to promote weight loss. Our studies define a hypothalamic switch that coordinates energy expenditure with feeding for the maintenance of energy balance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dodd, Garron T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andrews, Zane B. UNSPECIFIED orcid.org/0000-0002-9097-7944 UNSPECIFIED Simonds, Stephanie E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Michael, Natalie J. UNSPECIFIED UNSPECIFIED UNSPECIFIED DeVeer, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Spanswick, David UNSPECIFIED orcid.org/0000-0002-8129-8173 UNSPECIFIED Cowley, Michael A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tiganis, Tony UNSPECIFIED orcid.org/0000-0002-8065-9942 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-223040
DOI:	10.1016/j.cmet.2017.07.013
Journal or Publication Title:	Cell Metab.
Volume:	26
Number:	2
Page Range:	S. 375 - 401
Date:	2017
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1932-7420
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BROWN-ADIPOSE-TISSUE; PROTEIN-TYROSINE-PHOSPHATASE; AGOUTI-RELATED PROTEIN; INSULIN-RECEPTOR; LEPTIN ACTION; AGRP NEURONS; POMC NEURONS; PROOPIOMELANOCORTIN NEURONS; ARCUATE NUCLEUS; NEUROPEPTIDE-Y Multiple languages Cell Biology; Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22304