title: Life in the fat lane: seasonal regulation of insulin sensitivity, food intake, and adipose biology in brown bears.
abstract: Grizzly bears (Ursus arctos horribilis) have evolved remarkable metabolic adaptations including enormous fat accumulation during the active season followed by fasting during hibernation. However, these fluctuations in body mass do not cause the same harmful effects associated with obesity in humans. To better understand these seasonal transitions, we performed insulin and glucose tolerance tests in captive grizzly bears, characterized the annual profiles of circulating adipokines, and tested the anorectic effects of centrally administered leptin at different times of the year. We also used bear gluteal adipocyte cultures to test insulin and beta-adrenergic sensitivity in vitro. Bears were insulin resistant during hibernation but were sensitive during the spring and fall active periods. Hibernating bears remained euglycemic, possibly due to hyperinsulinemia and hyperglucagonemia. Adipokine concentrations were relatively low throughout the active season but peaked in mid-October prior to hibernation when fat content was greatest. Serum glycerol was highest during hibernation, indicating ongoing lipolysis. Centrally administered leptin reduced food intake in October, but not in August, revealing seasonal variation in the brain's sensitivity to its anorectic effects. This was supported by strong phosphorylated signal transducer and activator of transcription 3 labeling within the hypothalamus of hibernating bears; labeling virtually disappeared in active bears. Adipocytes collected during hibernation were insulin resistant when cultured with hibernation serum but became sensitive when cultured with active season serum. Heat treatment of active serum blocked much of this action. Clarifying the cellular mechanisms responsible for the physiology of hibernating bears may inform new treatments for metabolic disorders.
authors.affiliation: School of Biological Sciences, Washington State University, Pullman, WA, 99164, USA. kimberly.rigano@wsu.edu.
authors.forename: K S
authors.initials: KS
authors.lastname: Rigano
authors.affiliation: School of Biological Sciences, Washington State University, Pullman, WA, 99164, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Gehring
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, VBRB Room 205, MS7620, Pullman, WA, 99164, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Evans Hutzenbiler
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Chen
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164, USA.
authors.forename: O L
authors.initials: OL
authors.lastname: Nelson
authors.affiliation: Department of Movement Sciences, University of Idaho, Moscow, ID, 83844, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Vella
authors.affiliation: School of Biological Sciences, Washington State University, Pullman, WA, 99164, USA.|School of the Environment, Washington State University, Pullman, WA, 99164, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Robbins
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, VBRB Room 205, MS7620, Pullman, WA, 99164, USA. heiko@vetmed.wsu.edu.
authors.forename: H T
authors.initials: HT
authors.lastname: Jansen
mesh_terms: D054392:Adipokines / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004435:Eating; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006605:Hibernation / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood / Q000494:pharmacology; D050155:Lipogenesis / Q000502:physiology; D008066:Lipolysis / Q000502:physiology; D008297:Male; D011506:Proteins / Q000378:metabolism; D012621:Seasons; D001503:Ursidae / Q000502:physiology*
chemical_list: D054392:Adipokines; D020738:Leptin; D011506:Proteins; D005947:Glucose
keywords: Adiponectin; Adipose; Food intake; Glucose; Grizzly bear; Hibernation; Insulin; Leptin