title: Diminished metabolic responses to centrally-administered apelin-13 in diet-induced obese rats fed a high-fat diet.
abstract: The central administration of apelin, a recently identified adipokine, has been shown to affect food and water intake. The present study investigated whether body weight could affect an animal's response to apelin. The effects of centrally-administered apelin-13 on food and water intake, activity and metabolic rate were investigated in adult male diet-induced obese (DIO) rats fed either a high fat (32%) or control diet. Rats were administered i.c.v. apelin-13, 15-30 min prior to lights out, and food and water intake, activity and metabolic rate were assessed. Intracerebroventricular administration of apelin-13 decreased food and water intake and respiratory exchange ratio in DIO rats on the control diet, but had no effect in DIO rats on the high-fat diet. In an effort to identify potential central mechanisms explaining the observed physiological responses, the mRNA level of the apelin receptor, APJ, was examined in the hypothalamus. A high-fat diet induced an up-regulation of the expression of the receptor. Apelin induced a down-regulation of the receptor, but only in the DIO animals on the high-fat diet. In conclusion, we have demonstrated a diminished central nervous system response to apelin that is coincident with obesity.
authors.affiliation: Scripps Florida, Department of Molecular Therapeutics, Jupiter, FL, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Clarke
authors.forename: K W
authors.initials: KW
authors.lastname: Whitaker
authors.forename: T M
authors.initials: TM
authors.lastname: Reyes
mesh_terms: D000818:Animals; D000075244:Apelin Receptors; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004032:Diet; D004041:Dietary Fats; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D016207:Cytokines; D004041:Dietary Fats; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide