Shifts in metabolic fuel use coincide with maximal rates of ventilation and body surface rewarming in an arousing hibernator

Abstract

It is well established that hibernating mammals rely predominantly on lipid stores to fuel metabolism throughout the hibernation season. However, it is unclear if other endogenous fuels contribute to the rapid, ~400-fold increase in metabolic rate during the early phase of arousal from torpor. To investigate this issue, we used cavity ring-down spectroscopy, a technique that provides a real-time indication of fuel use by measuring the ratio of 13C to 12C in the exhaled CO2 of arousing 13-lined ground squirrels ( Ictidomys tridecemlineatus). We used infrared thermography to simultaneously measure ventilation and surface temperature change in various body regions, and we interpreted these data in light of changing plasma metabolite abundances at multiple stages of arousal from torpor. We found that hibernating squirrels use a combination of lipids and, likely, carbohydrates to fuel the initial ~60 min of arousal before switching to predominantly lipid oxidation. This fuel switch coincided with times of maximal rates of ventilation and rewarming of different body surface regions, including brown adipose tissue. Infrared thermography revealed zonal rewarming, whereby the brown adipose tissue region was the first to warm, followed by the thoracic and head regions and, finally, the posterior half of the body. Consistent with the results from cavity ring-down spectroscopy, plasma metabolite dynamics during early arousal suggested a large reliance on fatty acids, with a contribution from carbohydrates and glycerol. Because of their high oxidative flux rates and efficient O2 use, carbohydrates might be an advantageous metabolic fuel during the early phase of arousal, when metabolic demands are high but ventilation rates and, thus, O2 supply are relatively low.

Nitrogen recycling buffers against ammonia toxicity from skeletal muscle breakdown in hibernating arctic ground squirrels

“…One reason for this could be regional temperature differences during rewarming. 61 , 62 Tissues were collected 2 hours after IV bolus infusion during arousal; the head and thoracic region of the body warms more quickly than distal regions partially due to proximity of brown adipose tissue deposits and distal vasoconstriction. 61 Further, in AGS arousal, blood flow to the extremities significantly lags behind brain and organ blood flow, meaning that metabolic exchanges with circulation occur more quickly for the brain and visceral tissues than for the quadriceps.…”

“… 61 , 62 Tissues were collected 2 hours after IV bolus infusion during arousal; the head and thoracic region of the body warms more quickly than distal regions partially due to proximity of brown adipose tissue deposits and distal vasoconstriction. 61 Further, in AGS arousal, blood flow to the extremities significantly lags behind brain and organ blood flow, meaning that metabolic exchanges with circulation occur more quickly for the brain and visceral tissues than for the quadriceps. 62 If experiments had taken place during full arousal (T b >34°C) for a longer duration, we might have seen higher incorporation of labeled 15 N in all tissues and peripheral skeletal muscle that lags in rewarming.…”

Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability

“…The purpose of the energetically expensive arousals from torpor is not known, although, at least in lemurs, they appear to be compelled only in animals exhibiting torpid Tb < 30 • C (Dausmann et al, 2004). Clearly rates of biochemical reactions slow as Tb decreases during torpor, and differences in the thermal sensitivity of various reactions throughout the body leads to widespread changes, both increases and decreases, in the relative abundances of metabolites, transcripts and proteins across the torpor bout; the short, warm arousal periods are also highly dynamic, with changes between initial rewarming through the beginning of cooling when the next bout of torpor begins (Nelson et al, 2009;Epperson et al, 2011;Hindle et al, 2011Hindle et al, , 2014Jani et al, 2012;Grabek et al, 2015a;Bogren et al, 2017;D'Alessandro et al, 2017;Regan et al, 2019;Rice et al, 2020). While rewarming restores the slowed cellular processes and biochemical reaction rates of torpor in every system in the body, the detailed molecular mechanisms orchestrating these dynamics remain to be fully elucidated (see van Breukelen and Martin, 2015, and references therein).…”

Body Protein Sparing in Hibernators: A Source for Biomedical Innovation

“…Then, the increase in T b up to 12–16°C is accompanied by an increase in RQ to 1.0, indicating oxidation of carbohydrates, mainly by muscles for shivering thermogenesis (Mokrasch et al, 1960 ; Castex and Hoo-Paris, 1987 ; Heldmaier et al, 2004 ), and/or an evacuation of the CO 2 accumulated during torpor (Malan et al, 1988 ). A recent study has deepened the analysis in hibernating thirteen-lined ground squirrels (Regan et al, 2019 ). It has shown that a combination of lipids and carbohydrates is used during the initial ~60 min of arousal before switching to predominantly lipid oxidation.…”