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

Qian Gao, Gabor Mezei, Yongzhan Nie, Yan Rao, Cheol Soo Choi, Ingo Bechmann, Csaba Leranth, Dominique Toran-Allerand, Catherine A. Priest, James L. Roberts, Xiao Bing Gao, Charles Mobbs, Gerald I. Shulman, Sabrina Diano, Tamas L. Horvath

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300 Scopus citations

Abstract

Metabolic hormones, such as leptin, alter the input organization of hypothalamic circuits, resulting in increased pro-opiomelanocortin (POMC) tone, followed by decreased food intake and adiposity. The gonadal steroid estradiol can also reduce appetite and adiposity, and it influences synaptic plasticity. 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.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalNature Medicine
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2007

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C. S., Bechmann, I., Leranth, C., Toran-Allerand, D., Priest, C. A., Roberts, J. L., Gao, X. B., Mobbs, C., Shulman, G. I., Diano, S., & Horvath, T. L. (2007). Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nature Medicine, 13(1), 89-94. https://doi.org/10.1038/nm1525