Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight

Ronald P. Gaykema, Brandon A. Newmyer, Matteo Ottolini, Vidisha Raje, Daniel M. Warthen, Philip S. Lambeth, Maria Niccum, Ting Yao, Yiru Huang, Ira G. Schulman, Thurl E. Harris, Manoj K. Patel, Kevin W. Williams, Michael M. Scott

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake. Stimulation of GCG neurons had no effect on corticosterone secretion, body weight, or conditioned taste aversion. In the diet-induced obese state, the effects of GCG neuronal stimulation on gluconeogenesis were lost, while the food intake-lowering effects remained, resulting in reductions in body weight and adiposity. Our work suggests that GCG peptide-expressing neurons can alter feeding, metabolic rate, and glucose production independent of their effects on hypothalamic pituitary-adrenal (HPA) axis activation, aversive conditioning, or insulin secretion. We conclude that GCG neurons likely stimulate separate populations of downstream cells to produce a change in food intake and glucose homeostasis and that these effects depend on the metabolic state of the animal.

Original languageEnglish (US)
Pages (from-to)1031-1045
Number of pages15
JournalJournal of Clinical Investigation
Volume127
Issue number3
DOIs
StatePublished - Mar 1 2017

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Proglucagon
Eating
Body Weight
Neurons
Glucose
Peptides
Homeostasis
Rhombencephalon
Physiological Stress
Gluconeogenesis
Adiposity
Corticosterone
Pancreas
Anxiety
Insulin
Diet
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Gaykema, R. P., Newmyer, B. A., Ottolini, M., Raje, V., Warthen, D. M., Lambeth, P. S., ... Scott, M. M. (2017). Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight. Journal of Clinical Investigation, 127(3), 1031-1045. https://doi.org/10.1172/JCI81335

Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight. / Gaykema, Ronald P.; Newmyer, Brandon A.; Ottolini, Matteo; Raje, Vidisha; Warthen, Daniel M.; Lambeth, Philip S.; Niccum, Maria; Yao, Ting; Huang, Yiru; Schulman, Ira G.; Harris, Thurl E.; Patel, Manoj K.; Williams, Kevin W.; Scott, Michael M.

In: Journal of Clinical Investigation, Vol. 127, No. 3, 01.03.2017, p. 1031-1045.

Research output: Contribution to journalArticle

Gaykema, RP, Newmyer, BA, Ottolini, M, Raje, V, Warthen, DM, Lambeth, PS, Niccum, M, Yao, T, Huang, Y, Schulman, IG, Harris, TE, Patel, MK, Williams, KW & Scott, MM 2017, 'Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight', Journal of Clinical Investigation, vol. 127, no. 3, pp. 1031-1045. https://doi.org/10.1172/JCI81335
Gaykema RP, Newmyer BA, Ottolini M, Raje V, Warthen DM, Lambeth PS et al. Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight. Journal of Clinical Investigation. 2017 Mar 1;127(3):1031-1045. https://doi.org/10.1172/JCI81335
Gaykema, Ronald P. ; Newmyer, Brandon A. ; Ottolini, Matteo ; Raje, Vidisha ; Warthen, Daniel M. ; Lambeth, Philip S. ; Niccum, Maria ; Yao, Ting ; Huang, Yiru ; Schulman, Ira G. ; Harris, Thurl E. ; Patel, Manoj K. ; Williams, Kevin W. ; Scott, Michael M. / Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight. In: Journal of Clinical Investigation. 2017 ; Vol. 127, No. 3. pp. 1031-1045.
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