Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells

Paul Kievit, Jane K. Howard, Michael K. Badman, Nina Balthasar, Roberto Coppari, Hiroyuki Mori, Charlotte E. Lee, Joel K. Elmquist, Akihiko Yoshimura, Jeffrey S. Flier

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

Abstract

Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalCell Metabolism
Volume4
Issue number2
DOIs
StatePublished - Aug 2006

Keywords

  • HUMDISEASE
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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