title: The weight-reducing effect of an intracerebroventricular bolus injection of leptin in genetically obese fa/fa rats. Reduced sensitivity compared with lean animals.
abstract: The effect of different doses of leptin, given as an intracerebroventricular (ICV) bolus, on body weight gain and food intake was investigated during refeeding, following a 24-h fast in lean (FA/fa) rats. It was observed that ICV leptin resulted in a dose-dependent decrease in body weight gain, compared with vehicle injection, a difference that persisted for at least 6 days. This was associated with a transient reduction in food intake over the first 2 days after leptin injection. More importantly, the effect of leptin was also observed in genetically obese fa/fa rats but at the expense of two to ten times higher leptin concentrations, indicating the presence of decreased leptin sensitivity. Furthermore, ICV leptin injections were able to decrease neuropeptide Y (NPY) levels in the arcuate and paraventricular hypothalamic nuclei in both lean and genetically obese fa/fa rats, although a higher leptin dose was again needed in the obese group. These observations provide further evidence for the implication of NPY and leptin in a regulatory loop controlling body homeostasis. This loop is functional in lean and genetically obese fa/fa rats, provided that leptin levels in the central nervous system are high enough in the obese group, in particular. Since human obesity is frequently associated with elevated circulating leptin levels, a state of decreased leptin sensitivity (i.e., leptin resistance), similar to that described here in fa/fa rats, could possibly occur in human syndromes as well.
authors.affiliation: Laboratory of Metabolic Research, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Cusin
authors.forename: F
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
authors.forename: A
authors.initials: A
authors.lastname: Stricker-Krongrad
authors.forename: B
authors.initials: B
authors.lastname: Jeanrenaud
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005215:Fasting; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D020738:Leptin; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011922:Rats, Mutant Strains; D013851:Thinness; D013997:Time Factors
chemical_list: D020738:Leptin; D009478:Neuropeptide Y; D011506:Proteins