The Endogenous Actions of Hypothalamic Peptides on Brown Adipose Tissue Thermogenesis in the Rat

• Published in: Endocrinology (Philadelphia) 2010-09, Vol.151 (9), p.4236-4246
• Main Authors: Verty, Aaron N. A, Allen, Andrew M, Oldfield, Brian J
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose tissue (brown); Adipose Tissue, Brown - metabolism; Adipose Tissue, Brown - physiology; Animals; Benzoxazoles - pharmacology; Biological and medical sciences; Blotting, Western; Body fat; Body temperature; Body weight; Body Weight - drug effects; Brain stem; Eating - drug effects; Energy expenditure; Energy Metabolism - physiology; Feeding; Food intake; Fos protein; Fundamental and applied biological sciences. Psychology; Hypothalamic Hormones - antagonists & inhibitors; Hypothalamic Hormones - metabolism; Hypothalamic Hormones - physiology; Hypothalamus; Ion Channels - metabolism; Male; Melanin; Melanin-concentrating hormone; Melanins - antagonists & inhibitors; Melanins - metabolism; Melanins - physiology; Melanocortin; Melanocyte-Stimulating Hormones - pharmacology; Mitochondrial Proteins - metabolism; Orexin Receptors; Orexins; Peptides; Physical activity; Piperidines - pharmacology; Pituitary Hormones - antagonists & inhibitors; Pituitary Hormones - metabolism; Pituitary Hormones - physiology; Proteins; Pyrimidines - pharmacology; Random Allocation; Rats; Rats, Sprague-Dawley; Receptor, Melanocortin, Type 3 - antagonists & inhibitors; Receptor, Melanocortin, Type 4 - antagonists & inhibitors; Receptors; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, Neuropeptide - antagonists & inhibitors; Thermogenesis; Thermogenesis - drug effects; Thermogenesis - physiology; Uncoupling Protein 1; Urea - analogs & derivatives; Urea - pharmacology; Ventricles (cerebral); Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2009-1235

Although the neuronal pathways within the hypothalamus critical in controlling feeding and energy expenditure and projecting to brown adipose tissue (BAT) have been identified and their peptidergic content characterized, endogenous action of such peptides in the control of BAT activity has not been elucidated. Here male Sprague Dawley rats received infusions of either melanin-concentrating hormone antagonist (SNAP-7941) (1 μg/μl · h), orexin A receptor antagonist (SB-334867-A; 1 μg/μl · h), combined SB-334867-A (1 μg/μl · h), and SNAP-7941 (1 μg/μl · h), or melanocortin-3/4 receptor antagonist (SHU9119) (1 μg/μl · h) via an indwelling cannula in the lateral ventricle attached to sc implanted osmotic minipump. BAT temperature, physical activity, body weight, food intake, and changes in uncoupling protein (UCP)-1 were measured. SB-334867-A and SNAP-7941 significantly increased BAT temperature and UCP1 expression and reduced food intake and body weight. Combined infusion of SB-334867-A and SNAP-7941 produced a pronounced response that was greater than the addition of the individual effects in all parameters measured. SHU9119 significantly decreased BAT temperature and UCP1 expression and increased feeding and body weight. In a second series of experiments, the effect of SB-334867-A and SNAP-7941 alone or combination on the expression of the Fos protein was determined. SB-334867-A and SNAP-7941 increased Fos expression in key hypothalamic and brainstem feeding-related regions. In combination, these antagonists produced a greater than additive elevation of Fos expression in most of the regions evaluated. These findings support a role for endogenous orexigenic and anorexigenic hypothalamic peptides acting in concert to create a thermogenic tone via BAT activity. Endogenous orexigenic and anorexigenic hypothalamic peptides act in concert to create a thermogenic tone via brown adipose tissue activity.