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

• Main Author: Hapner, Hannah
• Other Authors: JANSEN, HEIKO, ROBBINS, CHARLES T, Dowd, W., KELLEY, JOANNA
• Format: Master Thesis
• Language: English
• Published: Washington State University 2021
• Subjects: Biology; Ursus arctos
• Online Access: https://doi.org/10.7273/000000056; https://rex.libraries.wsu.edu/esploro/outputs/graduate/Changing-lanes/99900587063801842; https://rex.libraries.wsu.edu/view/delivery/01ALLIANCE_WSU/12351080550001842/13351080540001842

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 exhibit the health consequences observed in obese humans. One example is the grizzly bear (Ursus arctos horribilis) that can have body fat contents >40%. It is known that hibernating bears survive by metabolizing their fat stores. Previous in vitro studies found that hibernation season adipocytes are insulin resistant and exhibit increased lipolysis as measured by extracellular glycerol. Yet, other aspects of cellular metabolism were not addressed, leaving this in vitro model incomplete. To this end, 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 (ECAR) and oxygen consumption rate (OCR) were used to calculate proton efflux rate (PER), and total ATP defined as both ATP from glycolysis and from mitochondrial respiration. Hibernation serum treated adipocytes lack metabolic flexibility and produce less ATP than active serum treated adipocytes. Insulin had minor influence on ATP production, but inhibited lipolysis in active but not hibernation serum treated adipocytes. This suggests that the reduction in glycolysis during hibernation is occurring downstream of insulin signaling and glucose uptake. These findings reveal a potent seasonal serum effect on metabolic capacity of bear adipocytes. Elucidation of responsible serum components involved and the cellular mechanisms that enable these influences may provide a novel avenue for the development of future treatments of human metabolic diseases.