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Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons.

Leptin, the adipose-derived hormonal signal of body energy stores, acts via the leptin receptor (LepRb) on neurons in multiple brain regions. We previously identified LepRb neurons in the lateral hypothalamic area (LHA), which are distinct from neighboring leptin-regulated melanin-concentrating hormone (MCH)- or orexin (OX)-expressing cells. Neither the direct synaptic targets of LHA LepRb neurons nor their potential role in the regulation of other LHA neurons has been determined, however. We thus generated several adenoviral and transgenic systems in which cre recombinase promotes the expression of the tracer, WGA (wheat germ agglutinin), and used these in combination with LepRb(cre) mice to determine the neuronal targets of LHA LepRb neurons. This analysis revealed that, although some LHA LepRb neurons project to dopamine neurons in the ventral tegmental area, LHA LepRb neurons also densely innervate the LHA where they directly synapse with OX, but not MCH, neurons. Indeed, few other LepRb neurons in the brain project to the OX-containing region of the mouse LHA, and direct leptin action via LHA LepRb neurons regulates gene expression in OX neurons. These findings thus reveal a major role for LHA leptin action in the modulation of OX neurons, suggesting the importance of LHA LepRb neurons in the regulation of OX signaling that is crucial to leptin action and metabolic control.

Pubmed ID: 20739548 RIS Download

Mesh terms: Animals | Female | Hypothalamic Area, Lateral | Intracellular Signaling Peptides and Proteins | Leptin | Male | Mice | Mice, Inbred C57BL | Mice, Obese | Mice, Transgenic | Neurons | Neuropeptides | Orexins | Receptors, Leptin

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK057768
  • Agency: NIDDK NIH HHS, Id: R01 DK055267
  • Agency: NCI NIH HHS, Id: P30 CA046592
  • Agency: NIDDK NIH HHS, Id: R01 DK057768
  • Agency: NIDDK NIH HHS, Id: DK078056
  • Agency: NIDDK NIH HHS, Id: R01 DK057768-12
  • Agency: NIDDK NIH HHS, Id: P30 DK036836
  • Agency: NIDDK NIH HHS, Id: R01 DK078056-02S1
  • Agency: NCI NIH HHS, Id: CA46592
  • Agency: NIDDK NIH HHS, Id: P60 DK020572
  • Agency: NIDDK NIH HHS, Id: R01 DK078056
  • Agency: NIDDK NIH HHS, Id: DK20572
  • Agency: NIDDK NIH HHS, Id: R01 DK078056-04
  • Agency: NIDDK NIH HHS, Id: P30 DK036836-169014
  • Agency: NIDDK NIH HHS, Id: P30 DK020572
  • Agency: NICHD NIH HHS, Id: T32 HD007048
  • Agency: NICHD NIH HHS, Id: T32 HD7048

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