Melanocortin-4 receptor mRNA is expressed in sympathetic nervous system outflow neurons to white adipose tissue

C. Kay Song, Raven M. Jackson, Ruth Babette Harris, Denis Richard, Timothy J. Bartness

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Energy balance results from the coordination of multiple pathways affecting energy expenditure and food intake. Candidate neuropeptides involved in energy balance are the melanocortins. Several species, including Siberian hamsters studied here, decrease and increase food intake in response to stimulation and blockade of the melanocortin 4-receptor (MC4-R). In addition, central application of the MC3/4-R agonist melanotan-II decreases body fat (increases lipolysis) beyond that accounted for by its ability to decrease food intake. Because an increase in the sympathetic nervous system drive to white adipose tissue (WAT) is the principal initiator of lipolysis, we tested whether the sympathetic outflow circuitry from brain to WAT contained MC4-R mRNA expressing cells. This was accomplished by labeling the sympathetic outflow to inguinal WAT using the pseudorabies virus (PRV), a transneuronal retrograde viral tract tracer, and then processing the brain for colocalization of PRV immunoreactivity with MC4-R mRNA, the latter assessed by in situ hybridization. MC4-R mRNA was impressively colocalized in PRV-labeled cells (approximately greater than 60%) in many brain areas across the neuroaxis, including those typically implicated in lipid mobilization (e.g., hypothalamic paraventricular, suprachiasmatic, arcuate and dorsomedial nuclei, lateral hypothalamic area), as well as those not traditionally identified with lipolysis (e.g., preoptic area, subzona incerta of the lateral hypothalamus, periaqueductal gray, solitary nucleus). These data provide compelling neuroanatomical evidence that could underlie a direct central modulation of the sympathetic outflow to WAT by the melanocortins through the MC4-Rs resulting in changes in lipid mobilization and adiposity.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume289
Issue number5 58-5
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Fingerprint

Receptor, Melanocortin, Type 4
White Adipose Tissue
Sympathetic Nervous System
Suid Herpesvirus 1
Lipolysis
Lipid Mobilization
Melanocortins
Lateral Hypothalamic Area
Neurons
Messenger RNA
Eating
Brain
Phodopus
Periaqueductal Gray
Arcuate Nucleus of Hypothalamus
Suprachiasmatic Nucleus
Solitary Nucleus
Preoptic Area
Groin
Paraventricular Hypothalamic Nucleus

Keywords

  • Lipolysis
  • Obesity
  • Pseudorabies virus
  • Siberian hamster

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Melanocortin-4 receptor mRNA is expressed in sympathetic nervous system outflow neurons to white adipose tissue. / Song, C. Kay; Jackson, Raven M.; Harris, Ruth Babette; Richard, Denis; Bartness, Timothy J.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 289, No. 5 58-5, 01.11.2005.

Research output: Contribution to journalArticle

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abstract = "Energy balance results from the coordination of multiple pathways affecting energy expenditure and food intake. Candidate neuropeptides involved in energy balance are the melanocortins. Several species, including Siberian hamsters studied here, decrease and increase food intake in response to stimulation and blockade of the melanocortin 4-receptor (MC4-R). In addition, central application of the MC3/4-R agonist melanotan-II decreases body fat (increases lipolysis) beyond that accounted for by its ability to decrease food intake. Because an increase in the sympathetic nervous system drive to white adipose tissue (WAT) is the principal initiator of lipolysis, we tested whether the sympathetic outflow circuitry from brain to WAT contained MC4-R mRNA expressing cells. This was accomplished by labeling the sympathetic outflow to inguinal WAT using the pseudorabies virus (PRV), a transneuronal retrograde viral tract tracer, and then processing the brain for colocalization of PRV immunoreactivity with MC4-R mRNA, the latter assessed by in situ hybridization. MC4-R mRNA was impressively colocalized in PRV-labeled cells (approximately greater than 60{\%}) in many brain areas across the neuroaxis, including those typically implicated in lipid mobilization (e.g., hypothalamic paraventricular, suprachiasmatic, arcuate and dorsomedial nuclei, lateral hypothalamic area), as well as those not traditionally identified with lipolysis (e.g., preoptic area, subzona incerta of the lateral hypothalamus, periaqueductal gray, solitary nucleus). These data provide compelling neuroanatomical evidence that could underlie a direct central modulation of the sympathetic outflow to WAT by the melanocortins through the MC4-Rs resulting in changes in lipid mobilization and adiposity.",
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