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Changing lanes: seasonal differences in cellular metabolism of adipocytes in grizzly bears (Ursus arctos horribilis)

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Abstract

Obesity is among the most prevalent of health conditions in humans leading to a multitude of metabolic pathologies such as type 2 diabetes and hyperglycemia. However, there are many wild animals that have large seasonal cycles of fat accumulation and loss that do not result in the health consequences observed in obese humans. One example is the grizzly bear (Ursus arctos horribilis) that can have body fat content > 40% that is then used as the energy source for hibernation. Previous in vitro studies found that hibernation season adipocytes exhibit insulin resistance and increased lipolysis. Yet, other aspects of cellular metabolism were not addressed, leaving this in vitro model incomplete. Thus, the current studies were performed to determine if the cellular energetic phenotype—measured via metabolic flux—of hibernating bears was retained in cultured adipocytes and to what extent that was due to serum or intrinsic cellular factors. Extracellular acidification rate and oxygen consumption rate were used to calculate proton efflux rate and total ATP defined as both ATP from glycolysis and from mitochondrial respiration. Hibernation adipocytes treated with hibernation serum produced less ATP and exhibited lower maximal respiration and glycolysis rates than active season adipocytes. These effects were reversed with serum from the opposite season. Insulin had little influence on total ATP production and lipolysis in both hibernation and active serum-treated adipocytes. Together, these results suggest that the metabolic suppression occurring in hibernation adipocytes are downstream of insulin signaling and likely due to a combined reduction in mitochondria number and/or function and glycolytic processes. Future elucidation of the serum components and the cellular mechanisms that enable alterations in mitochondrial function could provide a novel avenue for the development of treatments for human metabolic diseases.

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Acknowledgements

We are endlessly grateful to the many volunteers and supervisors working at the WSU Bear Center and to Jessie McCleary, Nina Woodford, and Gaylynn Clyde of the WSU Office of the Campus Veterinarian for helping to make this research possible. Thank you to Michael Saxton for his adipocyte transcription contributions. Thank you to Marina Savenkova for technical and moral support.

Funding

Funding was obtained from the International Association for Bear Research and Management.

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Authors and Affiliations

  1. School of Biological Sciences, College of Arts and Sciences, Washington State University, Pullman, WA, 99164, USA

    Hannah R. Hapner Hogan & Charles T. Robbins

  2. Department Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164, USA

    Brandon D. E. Hutzenbiler & Heiko T. Jansen

  3. School of the Environment, College of Agricultural, Human and Natural Resource Sciences, Washington State University, Pullman, WA, 99164, USA

    Brandon D. E. Hutzenbiler & Charles T. Robbins

Authors
  1. Hannah R. Hapner Hogan
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  2. Brandon D. E. Hutzenbiler
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  3. Charles T. Robbins
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  4. Heiko T. Jansen
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Contributions

HTJ and CTR obtained funding; HRHH, BDEH, and HTJ designed the study; HTJ, CTR, BDEH, and HRHH performed the blood and tissue sampling; HRHH and BDEH performed the metabolic flux analyses, lactate, pyruvate, and lipolysis measurements; HRHH, BDEH, and HTJ analyzed the data; The first draft of the manuscript was written by HRHH and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hannah R. Hapner Hogan or Heiko T. Jansen.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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IACUC ASAF #6546.

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Communicated by G. Heldmaier.

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Hogan, H.R.H., Hutzenbiler, B.D.E., Robbins, C.T. et al. Changing lanes: seasonal differences in cellular metabolism of adipocytes in grizzly bears (Ursus arctos horribilis). J Comp Physiol B 192, 397–410 (2022). https://doi.org/10.1007/s00360-021-01428-z

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