Cell Metabolism
Volume 26, Issue 2, 1 August 2017, Pages 375-393.e7
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Article
A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding

https://doi.org/10.1016/j.cmet.2017.07.013Get rights and content
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Highlights

  • Diurnal changes in hypothalamic TCPTP coordinate feeding with energy expenditure

  • Feeding represses hypothalamic TCPTP to increase energy expenditure

  • TCPTP inhibits insulin signaling in AgRP neurons to repress energy expenditure

  • Insulin signaling in AgRP neurons increases the browning of white fat

Summary

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

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

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