Abstract
Obesity is a worldwide pandemic with significant comorbidities. It is often accompanied by mild inflammation of the intestine followed by inflammation of metabolic tissues such as liver, adipose tissue, and skeletal muscle. Several laboratory models of obesity exist, but seasonal models like hibernators may be valuable for understanding the pathogenesis of obesity independent of genetic or high-fat diet-induced changes. As part of their annual cycle, obligate hibernators, like the 13-lined ground squirrel (Ictidomys tridecemlineatus), undergo a rapid shift from a lean to an obese state to store energy in the form of fat for their prolonged winter fast. Here, we show that ground squirrels gained mass steadily throughout the active season despite a drop in energy intake starting around 9 weeks post-hibernation. Glucose tolerance tests revealed a significant decrease in tolerance late in the active season. In visceral adipose, we found increases in adipocyte size, tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels. IL-6 levels also increased in liver and muscle and TNF-α increased in the ileum late in the active season. Levels of the anti-inflammatory cytokine, IL-10, decreased in visceral adipose and colon tissues around the same time. These data suggest metabolic inflammation develops along with adiposity late in the squirrels’ active season.
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Acknowledgements
The authors would like to thank Margot Elliott and Kelli Trester for help with animal husbandry and tissue collection. The authors gratefully acknowledge the support of the University of Wisconsin Oshkosh Faculty Development Grant program, the University of Wisconsin Oshkosh Office of Student Research and Creative Activity (OSRCA; Student-Faculty Collaborative Grant to Sonsalla), and the McNair Scholars program (grants to Love and Bojang) for funding this project.
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University of Wisconsin Oshkosh (USA) Faculty Development Grant program (Kurtz), University of Wisconsin Oshkosh (USA) Office of Student Research and Creative Activity (OSRCA; Student-Faculty Collaborative Grant to Sonsalla), and the McNair Scholars program (grants to Love and Bojang).
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MMS: helped design experiments, collected and analyzed data, wrote the majority of the manuscript. SLL, LJH, LNS, HMF, AB: helped with animal care, collection and analysis of data, responsible for analysis of specific tissues included in the study, wrote portions of the manuscript. KND: responsible for design of study (along with CCK) and edits of manuscript. CCK: responsible for design of study (along with KND), management of project, collection and analysis of data, writing and editing of manuscript, design of figures, mentoring students (MMS, SLL, LJH, LNS, HMF and AB) during project.
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The animal research outlined in this manuscript is approved under protocol #0026-000298 by the University of Wisconsin Oshkosh Animal Care and Use Committee.
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Sonsalla, M.M., Love, S.L., Hoh, L.J. et al. Development of metabolic inflammation during pre-hibernation fattening in 13-lined ground squirrels (Ictidomys tridecemlineatus). J Comp Physiol B 191, 941–953 (2021). https://doi.org/10.1007/s00360-021-01384-8
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DOI: https://doi.org/10.1007/s00360-021-01384-8