Chronic intraparaventricular nuclear administration of orexin A in male rats does not alter thyroid axis or uncoupling protein-1 in brown adipose tissue

• Published in: Regulatory peptides 2002-03, Vol.104 (1), p.61-68
• Main Authors: Russell, S.H, Small, C.J, Sunter, D, Morgan, I, Dakin, C.L, Cohen, M.A, Bloom, S.R
• Format: Article
• Language: English
• Subjects: Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Animals; Body Weight - drug effects; Carrier Proteins - administration & dosage; Carrier Proteins - metabolism; Carrier Proteins - pharmacology; Eating - drug effects; Hypocretin 1; Hypothalamic explants; Hypothalamic–pituitary thyroid axis; Injections, Intraventricular - methods; Intracellular Signaling Peptides and Proteins; Ion Channels; iPVN; Male; Membrane Proteins - metabolism; Mitochondrial Proteins; Neuropeptides - administration & dosage; Neuropeptides - pharmacology; Orexins; Pituitary Hormones - blood; Rats; Rats, Wistar; Thermogenesis; Thyroid Gland - drug effects; Thyrotropin - blood; Thyroxine - blood; Triiodothyronine - blood; Uncoupling Protein 1
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/S0167-0115(01)00349-4

Orexin A, synthesised in the posterolateral hypothalamus, has widespread distribution including the paraventricular nucleus (PVN), which is rich in thyrotropin-releasing hormone (TRH) neurones. Nerve fibres in the PVN synapse on neurones that send polysynaptic projections to brown adipose tissue (BAT), which is important in thermogenesis. A number of observations suggests orexin A may be involved in regulation of metabolism and thermogenesis. We investigated the effect of orexin A injected intracerebroventricularly (ICV) on thyroid-stimulating hormone (TSH) and thyroid hormones in male rats. We then examined the effect of chronic iPVN injections of orexin A on plasma TSH and uncoupling protein-1 (UCP-1) protein in BAT. Orexin A (3 nmol) administered ICV significantly suppressed plasma TSH at 10 and 90 min. Orexin A (0.3 nmol) administered into the PVN twice daily for 3 days significantly increased day-time 2-h food intake, but did not significantly alter nocturnal food intake. Though chronic iPVN orexin A altered diurnal food intake, there was no effect on 24-h food intake or body weight. Furthermore, orexin A administered chronically into the PVN did not alter UCP-1 level in BAT, or plasma hormones relative to saline injected animals. Chronic iPVN orexin A does not appear to influence thermogenesis through activation of UCP-1 or the thyroid axis.