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Functional implications of limited leptin receptor and ghrelin receptor coexpression in the brain.

http://www.ncbi.nlm.nih.gov/pubmed/21674492

The hormones leptin and ghrelin act in apposition to one another in the regulation of body weight homeostasis. Interestingly, both leptin receptor expression and ghrelin receptor expression have been observed within many of the same nuclei of the central nervous system (CNS), suggesting that these hormones may act on a common population of neurons to produce changes in food intake and energy expenditure. In the present study we explored the extent of this putative direct leptin and ghrelin interaction in the CNS and addressed the question of whether a loss of ghrelin signaling would affect sensitivity to leptin. Using histological mapping of leptin receptor and ghrelin receptor expression, we found that cells containing both leptin receptors and ghrelin receptors are mainly located in the medial part of the hypothalamic arcuate nucleus. In contrast, coexpression was much less extensive elsewhere in the brain. To assess the functional consequences of this observed receptor distribution, we explored the effect of ghrelin receptor deletion on leptin sensitivity. In particular, the responses of ad libitum-fed, diet-induced obese and fasted mice to the anorectic actions of leptin were examined. Surprisingly, we found that deletion of the ghrelin receptor did not affect the sensitivity to exogenously administrated leptin. Thus, we conclude that ghrelin and leptin act largely on distinct neuronal populations and that ghrelin receptor deficiency does not affect sensitivity to the anorexigenic and body weight-lowering actions of leptin.

Pubmed ID: 21674492 RIS Download

Mesh terms: Animals | Body Weight | Brain | Diet, High-Fat | Ghrelin | Leptin | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Neurons | Obesity | RNA, Messenger | Receptors, Ghrelin | Receptors, Leptin | Recombinant Fusion Proteins

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Associated grants

  • Agency: NIDDK NIH HHS, Id: K08 DK068069
  • Agency: NIDDK NIH HHS, Id: K08 DK068069-05
  • Agency: NIDDK NIH HHS, Id: K08DK068069
  • Agency: NIDA NIH HHS, Id: K99 DA024719-02
  • Agency: NIDA NIH HHS, Id: K99DA024719
  • Agency: NIDDK NIH HHS, Id: PL1 DK081182
  • Agency: NIDDK NIH HHS, Id: PL1 DK081182-01
  • Agency: NIDDK NIH HHS, Id: PL1DK081182
  • Agency: NIDA NIH HHS, Id: R01 DA024680
  • Agency: NIDA NIH HHS, Id: R01 DA024680-05
  • Agency: NIDDK NIH HHS, Id: R01 DK071320
  • Agency: NIDDK NIH HHS, Id: R01 DK071320-08
  • Agency: NIMH NIH HHS, Id: R01 MH085298
  • Agency: NIMH NIH HHS, Id: R01 MH085298-03
  • Agency: NIDA NIH HHS, Id: R01DA024680
  • Agency: NIDDK NIH HHS, Id: R01DK71320
  • Agency: NIMH NIH HHS, Id: R01MH085298
  • Agency: NIDDK NIH HHS, Id: RL1 DK081185
  • Agency: NIDDK NIH HHS, Id: RL1 DK081185-05
  • Agency: NIDDK NIH HHS, Id: RL1DK081185
  • Agency: NCRR NIH HHS, Id: UL1 RR024923
  • Agency: NCRR NIH HHS, Id: UL1 RR024923-01
  • Agency: NCRR NIH HHS, Id: UL1RR024923

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