Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue

Adriana Voss-Andreae, Jonathan G. Murphy, Kate L J Ellacott, Ronald C. Stuart, Eduardo A. Nillni, Roger D. Cone, Wei Fan

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The central melanocortin 4 receptor (MC4R) plays a critical role in energy homeostasis, although little is known regarding its role in the regulation of adaptive thermogenesis of brown adipose tissue (BAT). Here we show using retrograde transsynaptic tracing with attenuated pseudorabies virus coupled with dual-label immunohistochemistry that specific subsets of MC4R-expressing neurons in multiple nuclei of the central nervous system known to regulate sympathetic outflow polysynaptically connect with interscapular BAT (IBAT). Furthermore, we show that MC4R-/- and agouti-related peptide-treated mice are defective in HF diet-induced up-regulation of uncoupling protein 1 in IBAT. Additionally, MC4R-/- mice exposed to 4 C for 4 h exhibit a defect in up-regulation of uncoupling protein 1 levels in IBAT. Our results provide a neuroanatomic substrate for MC4R regulating sympathetically mediated IBAT thermogenesis and demonstrate that the MC4R is critically required for acute high-fat- and cold-induced IBAT thermogenesis.

Original languageEnglish (US)
Pages (from-to)1550-1560
Number of pages11
JournalEndocrinology
Volume148
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Receptor, Melanocortin, Type 4
Melanocortins
Brown Adipose Tissue
Thermogenesis
Up-Regulation
Suid Herpesvirus 1
Homeostasis
Central Nervous System
Immunohistochemistry
Fats
Diet
Neurons
Peptides

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Voss-Andreae, A., Murphy, J. G., Ellacott, K. L. J., Stuart, R. C., Nillni, E. A., Cone, R. D., & Fan, W. (2007). Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. Endocrinology, 148(4), 1550-1560. https://doi.org/10.1210/en.2006-1389

Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. / Voss-Andreae, Adriana; Murphy, Jonathan G.; Ellacott, Kate L J; Stuart, Ronald C.; Nillni, Eduardo A.; Cone, Roger D.; Fan, Wei.

In: Endocrinology, Vol. 148, No. 4, 04.2007, p. 1550-1560.

Research output: Contribution to journalArticle

Voss-Andreae, A, Murphy, JG, Ellacott, KLJ, Stuart, RC, Nillni, EA, Cone, RD & Fan, W 2007, 'Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue', Endocrinology, vol. 148, no. 4, pp. 1550-1560. https://doi.org/10.1210/en.2006-1389
Voss-Andreae A, Murphy JG, Ellacott KLJ, Stuart RC, Nillni EA, Cone RD et al. Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. Endocrinology. 2007 Apr;148(4):1550-1560. https://doi.org/10.1210/en.2006-1389
Voss-Andreae, Adriana ; Murphy, Jonathan G. ; Ellacott, Kate L J ; Stuart, Ronald C. ; Nillni, Eduardo A. ; Cone, Roger D. ; Fan, Wei. / Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. In: Endocrinology. 2007 ; Vol. 148, No. 4. pp. 1550-1560.
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