Regulation of Metabolism During Hibernation in Brown Bears (Ursus arctos): Involvement of Cortisol, PGC-1α and AMPK in Adipose Tissue and Skeletal Muscle

Chantal A. Vella, University of Idaho
O. Lynne Nelson, Washington State University
Heiko T. Jansen, Washington State University
Charles T. Robbins, Washington State University
Andrew E. Jensen, Washington State University
Silvana Constantinescu, Marymount California University
Marcia J. Abbott, Chapman University
Lorraine P. Turcotte, University of Southern California

NOTICE: this is the author’s version of a work that was accepted for publication in Comparative Biochemistry and Physiology, Part A: Molecular & Integrative Physiology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Comparative Biochemistry and Physiology, Part A: Molecular & Integrative Physiology, volume 240, in 2020.

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The purpose of this study was to investigate changes in expression of known cellular regulators of metabolism during hyperphagia (Sept) and hibernation (Jan) in skeletal muscle and adipose tissue of brown bears and determine whether signaling molecules and transcription factors known to respond to changes in cellular energy state are involved in the regulation of these metabolic adaptations. During hibernation, serum levels of cortisol, glycerol, and triglycerides were elevated, and protein expression and activation of AMPK in skeletal muscle and adipose tissue were reduced. mRNA expression of the co-activator PGC-1α was reduced in all tissues in hibernation whereas mRNA expression of the transcription factor PPAR-α was reduced in the vastus lateralis muscle and adipose tissue only. During hibernation, gene expression of ATGL and CD36 was not altered; however, HSL gene expression was reduced in adipose tissue. During hibernation gene expression of the lipogenic enzyme DGAT in all tissues and the expression of the FA oxidative enzyme LCAD in the vastus lateralis muscle were reduced. Gene and protein expression of the glucose transporter GLUT4 was decreased in adipose tissue in hibernation. Our data suggest that high cortisol levels are a key adaptation during hibernation and link cortisol to a reduced activation of the AMPK/PGC-1α/PPAR-α axis in the regulation of metabolism in skeletal muscle and adipose tissue. Moreover, our results indicate that during this phase of hibernation at a time when metabolic rate is significantly reduced metabolic adaptations in peripheral tissues seek to limit the detrimental effects of unduly large energy dissipation.