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Cell Metab. 2017 Aug 1;26(2):375-393.e7. doi: 10.1016/j.cmet.2017.07.013.

A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding.

Author information

1
Metabolic Disease and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
2
Metabolic Disease and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia; Department of Physiology, Monash University, Victoria 3800, Australia.
3
Monash Biomedical Imaging, Monash University, Victoria 3168, Australia.
4
Max Plank Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Gleueler Str. 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Str. 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; National Center for Diabetes Research (DZD), Ingolstädter Land Str. 1, 85764 Neuherberg, Germany.
5
Metabolic Disease and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia. Electronic address: tony.tiganis@monash.edu.

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.

KEYWORDS:

AgRP; Beige adipocyte; Diet-induced thermogenesis; Energy expenditure; Hypothalamus; Insulin; Obesity; Protein tyrosine phosphatase; TCPTP; White adipose tissue browning

PMID:
28768176
DOI:
10.1016/j.cmet.2017.07.013
[Indexed for MEDLINE]
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