The medial preoptic nucleus as a site of the thermogenic and metabolic actions of melanotan II in male rats

Boris Monge-Roffarello, Sebastien M. Labbe, Christophe Lenglos, Alexandre Caron, Damien Lanfray, Pierre Samson, Denis Richard

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The present study was designed to investigate the role of the medial preoptic nucleus (MPO) as a site of the thermogenic and metabolic effects of the α-melanocyte-stimulating hormone analog melanotan II (MTII). We also assessed the involvement of the dorsomedial hypothalamic nucleus (DMH) by investigating the effects of the MPO infusion of MTII in rats with DMH lesions produced by kainic acid. Infusion of MTII in the MPO led to increases in interscapular brown adipose tissue (iBAT) temperature and iBAT uptake of 14C-bromopalmitate. Both increases were blocked by DMH lesions. iBAT temperature increase (area under curve) and 14C-bromopalmitate uptake emerged as two correlated variables (r = 0.63, P < 0.001). DMH lesions also blocked MTII-induced expression of mRNAs coding for proteins involved in 1) thermogenesis [type II iodothyronine deiodinase (Dio2) and peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgc1α)], 2) lipolysis [hormone-sensitive lipase (Hsl)], and 3) lipogenesis [diacylglycerol-O-acyltransferase 2 (Dgat2), fatty acid synthase (Fas)], in iBAT of rats killed 1 h after MPO infusion of MTII. MTII also stimulated expression of genes in iWAT but only in rats with DMH lesions. These genes included glucose transporter member 4 (Glut4), glycerol-3-phosphate acyltransferase 3 (Gpat3), Dgat1, Dgat2, triglyceride lipase (Atgl), Hsl, and carnitine palmitoyltransferase 1β (Cpt1β). Altogether, the present results reveal the MPO as a site of the thermogenic and metabolic actions of MTII. They also contribute to establish the MPO-DMH duet as a significant target for melanocortins to modulate energy homeostasis.

Original languageEnglish (US)
Pages (from-to)R158-R166
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume307
Issue number2
DOIs
StatePublished - Jul 15 2014
Externally publishedYes

Keywords

  • Brown adipose tissue
  • Dorsomedial hypothalamus
  • Glucose uptake
  • Indirect calorimetry
  • Medial preoptic nucleus
  • Melanocortins
  • Nonesterified fatty acid uptake

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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