title: Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats.
abstract: Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg(-1)·h(-1))] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg(-1)·h(-1)) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats.
authors.affiliation: Veterans Affairs Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, 68105, USA. rogerr@creighton.edu
authors.forename: Roger
authors.initials: R
authors.lastname: Reidelberger
authors.forename: Alvin
authors.initials: A
authors.lastname: Haver
authors.forename: Prasanth K
authors.initials: PK
authors.lastname: Chelikani
authors.forename: Bettye
authors.initials: B
authors.lastname: Apenteng
authors.forename: Curtis
authors.initials: C
authors.lastname: Perriotte-Olson
authors.forename: Krista
authors.initials: K
authors.lastname: Anders
authors.forename: Sharalyn
authors.initials: S
authors.lastname: Steenson
authors.forename: James E
authors.initials: JE
authors.lastname: Blevins
mesh_terms: D000818:Animals; D001823:Body Composition / Q000502:physiology; D050218:Body Fat Distribution; D001835:Body Weight / Q000502:physiology; D031204:Caloric Restriction; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006963:Hyperphagia / Q000523:psychology; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000178:diet therapy* / Q000523:psychology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists; D014688:Venoms / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*; D015431:Weight Loss / Q000502:physiology*
chemical_list: C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D020738:Leptin; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide