Transplanted hypothalamic neurons restore leptin signaling and ameliorate obesity in db/db mice

Artur Czupryn, Yu-Dong Zhou, Xi Chen, David McNay, Matthew P Anderson, Jeffrey S Flier, Jeffrey D Macklis

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Evolutionarily old and conserved homeostatic systems in the brain, including the hypothalamus, are organized into nuclear structures of heterogeneous and diverse neuron populations. To investigate whether such circuits can be functionally reconstituted by synaptic integration of similarly diverse populations of neurons, we generated physically chimeric hypothalami by microtransplanting small numbers of embryonic enhanced green fluorescent protein-expressing, leptin-responsive hypothalamic cells into hypothalami of postnatal leptin receptor-deficient (db/db) mice that develop morbid obesity. Donor neurons differentiated and integrated as four distinct hypothalamic neuron subtypes, formed functional excitatory and inhibitory synapses, partially restored leptin responsiveness, and ameliorated hyperglycemia and obesity in db/db mice. These experiments serve as a proof of concept that transplanted neurons can functionally reconstitute complex neuronal circuitry in the mammalian brain.
Original languageEnglish
Pages (from-to)1133-1137
Number of pages5
JournalScience
Volume334
Issue number6059
DOIs
Publication statusPublished - 25 Nov 2011

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    Czupryn, A., Zhou, Y-D., Chen, X., McNay, D., Anderson, M. P., Flier, J. S., & Macklis, J. D. (2011). Transplanted hypothalamic neurons restore leptin signaling and ameliorate obesity in db/db mice. Science, 334(6059), 1133-1137. https://doi.org/10.1126/science.1209870