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Neuropsychopharmacology. 2018 Feb;43(3):627-637. doi: 10.1038/npp.2017.225. Epub 2017 Sep 18.

Glucagon-Like Peptide-1 Receptor Signaling in the Lateral Dorsal Tegmental Nucleus Regulates Energy Balance.

Author information

1
Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine, Department of Biological Sciences, University of Pennsylvania, Center for Neurobiology and Behavior, Philadelphia, PA, USA.
2
Neurobiology Section, University of Southern California, Los Angeles, CA, USA.
3
Human and Evolutionary Biology Section, University of Southern California, Los Angeles, CA, USA.

Abstract

The neurobiological substrates that mediate the anorectic effects of both endogenous glucagon-like peptide-1 (GLP-1) and exogenous GLP-1 receptor (GLP-1R) agonists are an active area of investigation. As the lateral dorsal tegmental nucleus (LDTg) expresses the GLP-1R and represents a potential neuroanatomical hub connecting the nucleus tractus solitarius (NTS), the major central source of GLP-1, with the other nuclei in the midbrain and forebrain, we tested the hypothesis that GLP-1R signaling in the LDTg controls food intake. Direct activation of LDTg GLP-1R suppresses food intake through a reduction in average meal size and independent of nausea/malaise. Immunohistochemical data show that GLP-1-producing neurons in the NTS project to the LDTg, providing anatomical evidence of endogenous central GLP-1 in the LDTg. Pharmacological blockade of LDTg GLP-1Rs with exendin-(9-39) dose-dependently increases food intake and attenuates the hypophagic effects of gastric distension. As GLP-1 mimetics are administered systemically in humans, we evaluated whether peripherally administered GLP-1R agonists access the LDTg to affect feeding. Immunohistochemical data show that a systemically administered fluorescent GLP-1R agonist accesses the LDTg and is juxtaposed with neurons. Additionally, blockade of LDTg GLP-1Rs attenuates the hypophagic effects of a systemic GLP-1R agonist. Together, these data indicate that LDTg GLP-1R signaling controls energy balance and underscores the role of the LDTg in integrating energy balance-relevant signals to modulate feeding.

PMID:
28920591
PMCID:
PMC5770766
DOI:
10.1038/npp.2017.225
[Indexed for MEDLINE]
Free PMC Article

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