Regulation of central melanocortin signaling by interleukin-1β

Jarrad M. Scarlett, Erin E. Jobst, Pablo J. Enriori, Darren D. Bowe, Ayesha K. Batra, Wilmon F. Grant, Michael A. Cowley, Daniel Marks

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Anorexia and involuntary weight loss are common and debilitating complications of a number of chronic diseases and inflammatory states. Proinflammatory cytokines, including IL-1β, are hypothesized to mediate these responses through direct actions on the central nervous system. However, the neural circuits through which proinflammatory cytokines regulate food intake and energy balance remain to be characterized. Here we report that IL-1β activates the central melanocortin system, a key neuronal circuit in the regulation of energy homeostasis. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) were found to express the type I IL-1 receptor. Intracerebroventricular injection of IL-1β induced the expression of Fos protein in ARC POMC neurons but not in POMC neurons in the commissural nucleus of the tractus solitarius. We further show that IL-1β increases the frequency of action potentials of ARC POMC neurons and stimulates the release of α-MSH from hypothalamic explants in a dose-dependent fashion. Collectively, our data support a model in which IL-1β increases central melanocortin signaling by activating a subpopulation of hypothalamic POMC neurons and stimulating their release of α-MSH.

Original languageEnglish (US)
Pages (from-to)4217-4225
Number of pages9
JournalEndocrinology
Volume148
Issue number9
DOIs
StatePublished - Sep 2007

Fingerprint

Melanocortins
Pro-Opiomelanocortin
Interleukin-1
AIDS-Related Complex
Neurons
Melanocyte-Stimulating Hormones
Cytokines
Arcuate Nucleus of Hypothalamus
Solitary Nucleus
Interleukin-1 Receptors
Anorexia
Action Potentials
Weight Loss
Homeostasis
Chronic Disease
Central Nervous System
Eating
Injections
Proteins

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Scarlett, J. M., Jobst, E. E., Enriori, P. J., Bowe, D. D., Batra, A. K., Grant, W. F., ... Marks, D. (2007). Regulation of central melanocortin signaling by interleukin-1β. Endocrinology, 148(9), 4217-4225. https://doi.org/10.1210/en.2007-0017

Regulation of central melanocortin signaling by interleukin-1β. / Scarlett, Jarrad M.; Jobst, Erin E.; Enriori, Pablo J.; Bowe, Darren D.; Batra, Ayesha K.; Grant, Wilmon F.; Cowley, Michael A.; Marks, Daniel.

In: Endocrinology, Vol. 148, No. 9, 09.2007, p. 4217-4225.

Research output: Contribution to journalArticle

Scarlett, JM, Jobst, EE, Enriori, PJ, Bowe, DD, Batra, AK, Grant, WF, Cowley, MA & Marks, D 2007, 'Regulation of central melanocortin signaling by interleukin-1β', Endocrinology, vol. 148, no. 9, pp. 4217-4225. https://doi.org/10.1210/en.2007-0017
Scarlett JM, Jobst EE, Enriori PJ, Bowe DD, Batra AK, Grant WF et al. Regulation of central melanocortin signaling by interleukin-1β. Endocrinology. 2007 Sep;148(9):4217-4225. https://doi.org/10.1210/en.2007-0017
Scarlett, Jarrad M. ; Jobst, Erin E. ; Enriori, Pablo J. ; Bowe, Darren D. ; Batra, Ayesha K. ; Grant, Wilmon F. ; Cowley, Michael A. ; Marks, Daniel. / Regulation of central melanocortin signaling by interleukin-1β. In: Endocrinology. 2007 ; Vol. 148, No. 9. pp. 4217-4225.
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