title: Effects of high affinity leptin antagonist on prolactin receptor deficient male mouse.
abstract: Hyperprolactinemia occurs during gestation and lactation with marked hyperphagia associated with leptin resistance. Prolactin (PRL) induces the expression of orexigenic neuropeptide Y (NPY) in hypothalamic dorsomedial nucleus (DMH) leading to hyperphagia. Along this line prolactin receptor deficient (PRLR-/-) mice are resistant to obesity under high fat diet due to increased energy expenditure. As these mice have an altered food intake, our objective was to test whether leptin is responsible for these characteristics. PRLR-/- male mice and control littermates were injected subcutaneously every other day with 12 mg/kg pegylated superactive mouse leptin antagonist (PEG-SMLA) for 3 weeks. We tested the effect of PEG-SMLA on body weight, food intake and metabolic parameters. The antagonist led to a rapid increase in body weight (20%) but increased adipose mass in PEG-SMLA treated mice was less pronounced in PRLR-/- than in WT mice. Food intake of PEG-SMLA-injected animals increased during the first week period of the experiment but then declined to a similar level of the control animals during the second week. Interestingly, PRLR-/- mice were found to have the same bone volume than those of control mice although PEG-SMLA increased bone mass by 7% in both strains. In addition, PEG-SMLA led to insulin resistance and glucose intolerance as well as an altered lipid profile in treated mice. Altogether, these results suggest that PRLR-/- mice respond to leptin antagonist similarly to the control mice, indicating no interaction between the actions of the two hormones.
authors.affiliation: Inserm U693, Le Kremlin-Bicêtre, France; Université Paris-Sud, Faculté de Médecine Paris-Sud, UMR-S693, Le Kremlin-Bicêtre, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Carré
authors.affiliation: The Hebrew University of Jerusalem, Institute of Biochemistry, Food Science and Nutrition, Rehovot, Israel.
authors.forename: Gili
authors.initials: G
authors.lastname: Solomon
authors.affiliation: The Hebrew University of Jerusalem, Institute of Biochemistry, Food Science and Nutrition, Rehovot, Israel.
authors.forename: Arieh
authors.initials: A
authors.lastname: Gertler
authors.affiliation: Inserm U693, Le Kremlin-Bicêtre, France; Université Paris-Sud, Faculté de Médecine Paris-Sud, UMR-S693, Le Kremlin-Bicêtre, France; Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
mesh_terms: D050154:Adiposity / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects; D018149:Glucose Intolerance / Q000139:chemically induced; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D020738:Leptin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011981:Receptors, Prolactin / Q000502:physiology*; D014129:Trabecular Meshwork / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D020738:Leptin; D011981:Receptors, Prolactin; C484843:pegylated leptin; D011092:Polyethylene Glycols