title: Weight Perturbation Alters Leptin Signal Transduction in a Region-Specific Manner throughout the Brain.
abstract: Diet-induced obesity (DIO) resulting from consumption of a high fat diet (HFD) attenuates normal neuronal responses to leptin and may contribute to the metabolic defense of an acquired higher body weight in humans; the molecular bases for the persistence of this defense are unknown. We measured the responses of 23 brain regions to exogenous leptin in 4 different groups of weight- and/or diet-perturbed mice. Responses to leptin were assessed by quantifying pSTAT3 levels in brain nuclei 30 minutes following 3 mg/kg intraperitoneal leptin. HFD attenuated leptin sensing throughout the brain, but weight loss did not restore central leptin signaling to control levels in several brain regions important in energy homeostasis, including the arcuate and dorsomedial hypothalamic nuclei. Effects of diet on leptin signaling varied by brain region, with results dependent on the method of weight loss (restriction of calories of HFD, ad lib intake of standard mouse chow). High fat diet attenuates leptin signaling throughout the brain, but some brain regions maintain their ability to sense leptin. Weight loss restores leptin sensing to some degree in most (but not all) brain regions, while other brain regions display hypersensitivity to leptin following weight loss. Normal leptin sensing was restored in several brain regions, with the pattern of restoration dependent on the method of weight loss.
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Morabito
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Yann
authors.initials: Y
authors.lastname: Ravussin
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Bridget R
authors.initials: BR
authors.lastname: Mueller
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Alicja A
authors.initials: AA
authors.lastname: Skowronski
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Kylie S
authors.initials: KS
authors.lastname: Foo
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Samuel X
authors.initials: SX
authors.lastname: Lee
authors.affiliation: AstraZeneca, R&D Disease Area Diabetes/Obesity, Mölndal, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Lehmann
authors.affiliation: AstraZeneca, R&D Disease Area Diabetes/Obesity, Mölndal, Sweden.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hjorth
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Lori M
authors.initials: LM
authors.lastname: Zeltser
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Charles A
authors.initials: CA
authors.lastname: LeDuc
authors.affiliation: Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D004032:Diet; D002149:Energy Intake; D004734:Energy Metabolism; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin