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Journal of Comparative Physiology B

, Volume 187, Issue 4, pp 649–676 | Cite as

Life in the fat lane: seasonal regulation of insulin sensitivity, food intake, and adipose biology in brown bears

  • K. S. RiganoEmail author
  • J. L. Gehring
  • B. D. Evans Hutzenbiler
  • A. V. Chen
  • O. L. Nelson
  • C. A. Vella
  • C. T. Robbins
  • H. T. JansenEmail author
Original Paper

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.

Keywords

Grizzly bear Hibernation Adipose Glucose Insulin Leptin Adiponectin Food intake 

Abbreviations

Tb

Body temperature

T2DM

Type 2 diabetes mellitus

WAT

White adipose tissue

pSTAT3

Phosphorylated signal transducer and activator of transcription 3

ivITT

Intravenous insulin tolerance tests

oGTT

Oral glucose tolerance tests

NP40

Tergitol-type NP-40

PMSF

Phenylmethylsulfonyl fluoride

AKT1

Protein kinase B

GSK3α, GSK3β

Glycogen synthase kinase-3

IGF1R

Insulin-like growth factor 1 receptor

IR

Insulin receptor

IRS1

Insulin receptor substrate-1

mTOR

Mammalian target of rapamycin

70S6K

Ribosomal protein S6 kinase

PTEN

Phosphatase and tensin homolog

RPS6

Ribosomal protein S6

TSC2

Tuberous sclerosis complex-2

rh-leptin

Recombinant human leptin

aCSF

Artificial cerebrospinal fluid

BSA

Bovine serum albumin

2-DG

2-Deoxyglucose

RT qPCR

Real time quantitative PCR

ADRB2

β2-Adrenergic receptor

LEP

Leptin

LEPR

Leptin receptor

ATGL

Adipose triglyceride lipase

ADRB1

β1-Adrenergic receptor

ADRB3

β3-Adrenergic receptor

CNS

Central nervous system

Notes

Acknowledgements

Funding was provided by Amgen Inc., the Interagency Grizzly Bear Committee, the Raili Korkka Brown Bear Endowment, the Bear Research and Conservation Endowment, and a National Science Foundation Graduate Research Fellowship (KSR, 1347943). We thank Danielle Rivet, Joy Erlenbach, Dr. Monica Bando and the other dedicated researchers at WSU’s Bear Research, Education, and Conservation Center for their assistance in data collection and captive bear care. We would also like to thank Jamie Gaber and Marina Savenkova for technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts.

Data sharing statement

Specified raw data files used for analysis have been uploaded to Dryad Digital Repository for public access (doi: 10.5061/dryad.sc38b).

Supplementary material

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Supplementary material 1 (TIFF 6078 kb)
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Supplementary material 2 (TIFF 6078 kb)
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Supplementary material 3 (TIFF 6078 kb)
360_2016_1050_MOESM4_ESM.docx (18 kb)
Supplementary material 4 (DOCX 17 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • K. S. Rigano
    • 1
    Email author
  • J. L. Gehring
    • 1
  • B. D. Evans Hutzenbiler
    • 2
  • A. V. Chen
    • 3
  • O. L. Nelson
    • 3
  • C. A. Vella
    • 4
  • C. T. Robbins
    • 1
    • 5
  • H. T. Jansen
    • 2
    Email author
  1. 1.School of Biological SciencesWashington State UniversityPullmanUSA
  2. 2.Department of Integrative Physiology and NeuroscienceWashington State UniversityPullmanUSA
  3. 3.Department of Veterinary Clinical Sciences, College of Veterinary MedicineWashington State UniversityPullmanUSA
  4. 4.Department of Movement SciencesUniversity of IdahoMoscowUSA
  5. 5.School of the EnvironmentWashington State UniversityPullmanUSA

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