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Cell Metab. 2014 Oct 7;20(4):639-49. doi: 10.1016/j.cmet.2014.07.022. Epub 2014 Aug 28.

The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus.

Author information

1
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
2
Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Ann Arbor, Michigan 48105, USA.
3
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
4
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: simon.luckman@manchester.ac.uk.

Abstract

Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase energy expenditure. Some of the cellular pathways mediating leptin's anorectic actions are identified, but those mediating the thermogenic effects have proven more difficult to decipher. We define a population of neurons in the dorsomedial hypothalamic nucleus (DMH) containing the RFamide PrRP, which is activated by leptin. Disruption of Lepr selectively in these cells blocks thermogenic responses to leptin and causes obesity. A separate population of leptin-insensitive PrRP neurons in the brainstem is required, instead, for the satiating actions of the gut-derived hormone cholecystokinin (CCK). Global deletion of PrRP (in a loxSTOPlox-PrRP mouse) results in obesity and attenuated responses to leptin and CCK. Cre-recombinase-mediated reactivation of PrRP in brainstem rescues the anorectic actions of CCK, but reactivation in the hypothalamus is required to re-establish the thermogenic effect of leptin.

PMID:
25176149
PMCID:
PMC4192552
DOI:
10.1016/j.cmet.2014.07.022
[Indexed for MEDLINE]
Free PMC Article

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