Leptin and insulin act on POMC neurons to promote the browning of white fat

Garron T. Dodd, Stephanie Decherf, Kim Loh, Stephanie E. Simonds, Florian Wiede, Eglantine Balland, Troy L. Merry, Heike Münzberg, Zhong Yin Zhang, Barbara B. Kahn, Benjamin G. Neel, Kendra K. Bence, Zane B. Andrews, Michael A. Cowley, Tony Tiganis

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)88-104
Number of pages17
JournalCell
Volume160
Issue number1-2
DOIs
StatePublished - Jan 15 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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. (2015). Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell, 160(1-2), 88-104. https://doi.org/10.1016/j.cell.2014.12.022