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Leptin and Insulin Act on POMC Neurons to Promote the Browning of White Fat
Open accessAbstract
The primary task of white adipose tissue (WAT) is the storage of lipids. However, "beige" adipocytes also exist in WAT. Beige adipocytes burn fat and dissipate the energy as heat, but their abundance is diminished in obesity. Stimulating beige adipocyte development, or WAT browning, increases energy expenditure and holds potential for combating metabolic disease and obesity. Here, we report that insulin and leptin act together on hypothalamic neurons to promote WAT browning and weight loss. Deletion of the phosphatases PTP1B and TCPTP enhanced insulin and leptin signaling in proopiomelanocortin neurons and prevented diet-induced obesity by increasing WAT browning and energy expenditure. The coinfusion of insulin plus leptin into the CNS or the activation of proopiomelanocortin neurons also increased WAT browning and decreased adiposity. Our findings identify a homeostatic mechanism for coordinating the status of energy stores, as relayed by insulin and leptin, with the central control of WAT browning.
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“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 [108]
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“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 [108]
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Metadata
- Authors
- Dodd, G. T., Decherf, S., Loh, K., Simonds, S. E., Wiede, F., Balland, E., Merry, T. L., Münzberg, H., Zhang, Z.-Y., Kahn, B. B., Neel, B. G., Bence, K. K., Andrews, Z. B., Cowley, M. A., & Tiganis, T.
- Affiliations
- Monash University (AU)
- Pennington Biomedical Research Center (US)
- Indiana University Indianapolis (US)
- Beth Israel Deaconess Medical Center (US)
- University of Toronto (CA)
- University of Pennsylvania (US)
- Corresponding author
- Tiganis, Tony
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 160
- Issue
- 1-2
- Pages
- 88-104
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4453004
- OpenAlex
- W2078409165
- Cited by
- 398
- References
- 59
- Citations by year
- 2026: 15 · 2025: 30 · 2024: 33 · 2023: 28 · 2022: 29 · 2021: 46 · 2020: 35 · 2019: 37 · 2018: 38 · 2017: 34 · 2016: 42 · 2015: 31
- FWCI
- 35.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R37CA049152, R01CA126937, R01CA069202)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082417, P01DK056116, R01DK098002)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, insulin, white adipose tissue browning, beige adipocytes, POMC neurons, hypothalamus, PTP1B, TCPTP, diet-induced obesity, energy expenditure, weight loss
- MeSH terms
- Animals, Body Temperature Regulation, Adipose Tissue, Brown, Insulin, Mice, Inbred C57BL, Neurons, Obesity, Pro-Opiomelanocortin, Mice, Knockout, Leptin, Adiposity, Adipose Tissue, White, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Protein Tyrosine Phosphatase, Non-Receptor Type 2
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