A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding

Garron T. Dodd, Zane B. Andrews, Stephanie E. Simonds, Natalie J. Michael, Michael DeVeer, Jens C. Brüning, David Spanswick, Michael A. Cowley, Tony Tiganis

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)375-393
Number of pages20
JournalCell Metabolism
Volume26
Issue number2
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

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

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