A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding
Open accessAbstract
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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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.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [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.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [109]
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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
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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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