Cited by 67Regulation of Appetite and ObesityAdipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic Diseases

A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding

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Dodd, Garron T., Andrews, Zane B., Simonds, Stephanie E., Michael, Natalie J., DeVeer, Michael, Brüning, Jens C., Spanswick, David, Cowley, Michael A. +1 more·2017·Cell Metabolism

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.

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Crossref · 10.1016/j.cmet.2017.07.013

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  • The actions of leptin and insulin in POMC neurons can be triggered by a decrease in hypothalamic TCPTP, a negative regulator of insulin signaling, to further increase browning of WAT and energy expenditure.

    “The actions of leptin and insulin in POMC neurons can also be triggered by a decrease in the hypothalamic levels of T‐cell protein tyrosine phosphatase (TCPTP), which is a negative regulator of insulin signaling, to further increase the browning of WAT and energy expenditure 108, 109.”
  • Leptin can increase energy expenditure by inducing BAT activation.

    “Apart from its role in the regulation of food intake described above, leptin can increase energy expenditure by inducing BAT activation.”

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Authors
Dodd, G. T., Andrews, Z. B., Simonds, S. E., Michael, N. J., DeVeer, M., Brüning, J. C., Spanswick, D., Cowley, M. A., & Tiganis, T.
Affiliations
  • Monash University (AU)
  • University of Cologne (DE)
Corresponding author
Tiganis, Tony
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2017-08
Volume
26
Issue
2
Pages
375-393.e7
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2739586877
Cited by
66
References
86
Citations by year
2026: 2 · 2025: 10 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 3 · 2019: 8 · 2018: 9 · 2017: 2
FWCI
3.70
Type
journal article
Language
en
Update notices
erratum (2017-09-05)
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • Monash University Research Portal (Monash University) (submittedVersion, other-oa)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • Diabetes Australia Research Trust
  • National Imaging Facility
  • Diabetes Australia
  • National Health and Medical Research Council
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
TCPTP, phosphatase, hypothalamus, beige adipocytes, white adipose tissue browning, energy expenditure, feeding, insulin signaling, glucocorticoids, fasting, diet-induced obesity, energy balance, weight loss
MeSH terms
Animals, Eating, Energy Metabolism, Hypothalamus, Mice, Transgenic, Neuropeptide Y, Obesity, Mice, Agouti-Related Protein, Protein Tyrosine Phosphatase, Non-Receptor Type 2

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