Seasonal Cold Exposure Modulates Metabolic Phenotype and Mitochondrial Function in Obese Golden‐Mantled Ground Squirrels
Authors: Heim Ashley B , Lashbrook Melanie A , Rosales Susana A , Wakefield Jordan B , Florant Gregory L , Chicco Adam J 
Published: June 2021

Golden‐mantled ground squirrels (Callospermophilus lateralis; GMGS) develop seasonal obesity in early autumn, which provides essential fuel stores for successful hibernation through the long Rocky Mountain winter. This is facilitated by circannual variations in hormones regulating food intake and metabolism independent of environmental cues, but is accompanied by a decrease in ambient temperature that might also influence metabolic phenotype. The present study evaluated the effect of seasonal cold exposure on body composition, glucose tolerance and tissue mitochondrial function in obese GMGS prior to hibernation. We hypothesized that cold exposure compliments seasonal adiposity by altering metabolic and mitochondrial parameters that further optimize physiological preparation for hibernation. Adult GMGS were captured in mid‐summer and transferred to an animal facility maintained at 22 deg C, and provided standard rodent chow (Harlan 2918) and water ad libitum. Animals were allowed to acclimate to the new environment for at least 4 weeks before being sacrificed for baseline evaluation as lean summer controls (Lean; N = 7) or randomized to continue on the ab libitum diet for 4–6 more weeks at 22 deg C (Ob‐warm; N = 4) or 15 deg C to simulate the seasonal decrease in temperature normally encountered by animals in the wild (Ob‐cold; N = 6). Lean animals had lower body weight (247 ± 12 g) and body fat (25 ± 4 %) compared to obese groups, with no difference between Ob‐warm (312 ± 16 g; 47 ± 2 % fat) and Ob‐cold (302 ± 23 g; 47 ± 5 % fat). Blood glucose disposal following a 2 g/kg i.p. glucose challenge was much more rapid in Lean compared to Ob groups, and greater in Ob‐cold vs. Ob‐warm animals, indicating an expected decrease in glucose tolerance with obesity that was attenuated by cold exposure. Liver mitochondria from obese animals exhibited greater maximal ADP‐dependent (OXPHOS) respiration vs. Lean with both carbohydrate (pyruvate) and lipid (palmitoylcarnitine) substrates. Cold exposure attenuated the increase in lipid OXPHOS in obese animals, but had no effects on carbohydrate OXPHOS capacity. Conversely, in cardiac mitochondria, maximal and carbohydrate OXPHOS capacity was similar between Lean and Ob‐warm groups, but significantly elevated in Ob‐cold animals. In muscle mitochondria, obesity reduced carbohydrate OXPHOS capacity, with no significant effects on lipid OXPHOS and no modulation by cold exposure. Taken together, these data suggest that seasonal cold exposure modifies metabolic responses to obesity in pre‐hibernating GMGSs, leading to improvements in systemic glucose disposal, tissue‐specific alterations in mitochondrial substrate utilization, and enhancement of cardiac mitochondrial OXPHOS capacity. These adaptations might serve to optimize systemic preparation for prolonged hypometabolism and reliance on lipid stores during hibernation, and provide insight into the metabolic effects of physiologic cold exposure with potential relevance to obesity‐related metabolic disorders.Support or Funding InformationFunding for this work was provided in part by grants from the USDA and American Heart Association to AJC.