Letter abstract

Nature Medicine 13, 89 - 94 (2006)
Published online: 31 December 2006 | doi:10.1038/nm1525

Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals

Qian Gao1, Gabor Mezei1, Yongzhan Nie1, Yan Rao1, Cheol Soo Choi2, Ingo Bechmann3, Csaba Leranth1, Dominique Toran-Allerand4, Catherine A Priest5, James L Roberts6, Xiao-Bing Gao1, Charles Mobbs5, Gerald I Shulman2, Sabrina Diano1,7 & Tamas L Horvath1,7,8


Metabolic hormones, such as leptin, alter the input organization of hypothalamic circuits1, 2, 3, resulting in increased pro-opiomelanocortin (POMC) tone, followed by decreased food intake and adiposity. The gonadal steroid estradiol can also reduce appetite and adiposity4, 5, and it influences synaptic plasticity6. Here we report that estradiol (E2) triggers a robust increase in the number of excitatory inputs to POMC neurons in the arcuate nucleus of wild-type rats and mice. This rearrangement of synapses in the arcuate nucleus is leptin independent because it also occurred in leptin-deficient (ob/ob) and leptin receptor–deficient (db/db) mice, and was paralleled by decreased food intake and body weight gain as well as increased energy expenditure. However, estrogen-induced decrease in body weight was dependent on Stat3 activation in the brain. These observations support the notion that synaptic plasticity of arcuate nucleus feeding circuits is an inherent element in body weight regulation and offer alternative approaches to reducing adiposity under conditions of failed leptin receptor signaling.

  1. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
  2. Department of Internal Medicine and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
  3. Institute for Clinical Neuroanatomy, Johann Wolfgang Goethe-University, 60 596 Frankfurt/Main, Germany.
  4. Department of Obstetrics and Gynecology, Department of Pathology and Cell Biology, and Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
  5. Fishberg Research Center for Neurobiology and Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, New York, New York 10029, USA.
  6. Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
  7. Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
  8. Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Correspondence to: Tamas L Horvath1,7,8 e-mail: tamas.horvath@yale.edu

Correspondence to: Qian Gao1 e-mail: qian.gao@yale.edu


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