1. Shivering Thermogenesis is Limited by Glycogen Depletion
Authors: Mikayla Wohlleben, Alexa Comeau
Simon Fraser University – Fall 2016
BPK 432 – Physiological Basis of Temperature Regulation
November 21st, 2016

2. Hypotheses
Our hypothesis for this point presentation is that shivering heat production is limited by glycogen depletion.
The hypothesis for the counterpoint presentation is that shivering heat production is not limited by glycogen depletion.

3. Support for the Point Hypothesis
In a study by Haman et al., the relative contributions of carbohydrate (CHO), lipid, and protein oxidation towards total heat production (Hprod) were compared during low- and moderate- intensity shivering.1
Glycogen utilization as a percentage of total heat production was seen to increase significantly for moderate intensity shivering.1
Lipid utilization remained relatively constant and protein utilization decreased throughout the cold exposure.1 Since these rates remained relatively unchanged, the observed 100 W metabolic rate increase from the low to moderate shivering intensity was attributed solely to glycogen oxidation.1  
Data obtained from Haman et al. (1).

4. Support for the Point Hypothesis
In the figure on the previous slide, CHO encompasses both muscle glycogen and plasma glucose. 1
In this graph, plasma glucose oxidation is seen to be much more strongly stimulated by moderate shivering, but the relative contribution of this pathway to total heat generation remains minor (<15% Hprod). 1
Since glycogen provided 40% the total heat production, it can be concluded that glycogen is dominant for higher intensity shivering responses. 1
Data obtained from Haman et al. (1).

5. Support for the Point Hypothesis
In a study by LeBlanc and Labrie, it was seen that repeated cold exposures caused significantly reduced glycogen levels in the liver immediately after the series of cold stresses, indicating that glycogen was the fuel source being utilized for thermogenesis.2
Glycogen levels were significantly elevated in the liver, tibialis, and soleus from their initial levels in all conditions that led to glycogen depletion when measured 24 hours after the repeated cold stresses.2
Data obtained from LeBlanc and Labrie. (2).

6. Support for the Point Hypothesis
Data obtained from LeBlanc and Labrie. (2).
Referring to the graph, the cold-exposed mice tested on the same day all became hypothermic before hour 3, whereas the mice tested 24-hours later did not all become hypothermic until 4 hours and 30 minutes.2 This increased time between groups demonstrates a significant resistance to hypothermia.2
Increased glycogen storage indicated by the previous figure, in combination with this increased cold resistance, shows that glycogen was vital to the body's ability to adapt to cold exposure. 2 This likely represents a compensatory mechanism to better produce subsequent thermogenic responses.2

7. Support for the Point Hypothesis
Data obtained from Martineau and Jacobs. (3).
Data obtained from Martineau and Jacobs. (3).
In a study by Martineau and Jacobs, it was seen that post-immersion muscle glycogen levels were depleted compared to pre-immersion values. 3
It was found that reduced availability of muscle glycogen was associated with more rapid body cooling rates.3 This increase in cooling rate indicated that depleted glycogen stores inhibited normal thermogenic responses, therefore glycogen was seen to have a critical role in the body's ability to adapt to cold exposure. 3
Energy expenditure during the first 30 minutes of cold water immersion was also decreased in low- compared to both normal- and high-glycogen conditions.3 This is likely a direct result of decreased glycogen, which proves its limiting action towards cold tolerance, and therefore thermogenesis.3

8. Refuting of Evidence in Support of the Counterpoint Hypothesis
In a study by Neufer et al., post- hypothermic re-warming was seen to be unimpaired by low glycogen levels and individuals spontaneously re-warmed despite this depletion, showing that thermogenic re- warming was not reliant on glycogen.4
Data obtained from Neufer et al. (4)

9. Refuting of Evidence in Support of the Counterpoint Hypothesis
In their experiments, glycogen was only measured in the vastus lateralis and assumptions were made regarding the glycogen content in other muscles.4 This assumed uniformity of glycogen utilization across all muscle groups, which is likely inaccurate in reflecting true glycogen utilization rates.
Shivering was not measured and the relative shivering muscle groups went undetermined.4 This did not demonstrate the relative contributions of muscle groups towards shivering thermogenesis and therefore we cannot conclude where and by how much glycogen is utilized for shivering.4
Though the purpose of this study was to assess the influence of depleted glycogen levels on passive re-warming, the relative contribution of shivering thermogenesis towards this process remains uncertain.4

10. Refuting of Evidence in Support of the Counterpoint Hypothesis
Data obtained from Young et al. (5).
In a study by Young et al., after cold water immersion, body cooling rate and metabolic heat production, as seen in the graph, were not altered by substantial reductions in muscle glycogen levels.5
Hemoglobin and hematocrit concentrations were calculated to which a reduction in plasma volume by approximately 8% was estimated.5 However, their was uncertainty in the accuracy of this estimate, and therefore plasma metabolite concentrations were not corrected for changes in plasma volume.5 Plasma metabolites included free fatty acids, lactate, glycerol, and glucose.5
Failure to correct metabolite concentrations likely has negative implications for their conclusions regarding the increased availability of metabolic substrates other than glycogen for the fueling of shivering thermogenesis.5

11. Refuting of Evidence in Support of the Counterpoint Hypothesis
Postimmersion glycogen concentrations were not significantly different from preimmersion values for either the low or high muscle glycogen.5
It was assumed that the vastus lateralis glycogen content was representative of glycogen in other muscle groups and concluded that glycogen was reduced in several major muscle groups.5 However, this was clearly not supported since they only measured the vastus lateralis.5
It cannot be concluded that muscle glycogen is not a limiting substrate for shivering thermogenesis, since it was unknown whether the vastus lateralis participated in the observed shivering responses.5
Data obtained from Young et al. (5).

12. Refuting of Evidence in Support of the Counterpoint Hypothesis
In a study by Haman et al., it was concluded that large changes in glycogen reserves had no effect on thermogenesis during sustained shivering, and heat production of glycogen depleted individuals was not compromised.6
The focus was on muscle glycogen status, but glycogen concentrations were not directly measured in this study.6
The dietary and exercise regimen was assumed to have the desired impact on glycogen reserves based on the protocols5 from other studies.6
Due to the shortcomings of the approach towards calculating shivering endurance, the researchers admit that after 2 hours of shivering there could be a significant shift in fuel selection to conserve glycogen.6
This sparing effect would support the point that glycogen may be a limiting fuel substrate for shivering thermogenesis.
Data obtained from Haman et al. (6).

13. Conclusion
The evidence supports our hypothesis that shivering heat production is limited by glycogen depletion, and the evidence is overwhelmingly against the hypothesis that shivering heat production is not limited by glycogen depletion.

14. References
1. Haman F, Peronnet F, Kenny GP, Massicotte D, Lavoie C, Weber JM. Partitioning oxidative fuels during cold exposure in humans: muscle glycogen becomes dominant as shivering intensifies. J Physiol. 2005;566:
2. LeBlanc J, LaBrie A. Glycogen and non-specific adaptation to cold. J Appl Physiol. 1981;51(6):
3. Martineau L, Jacobs I. Muscle glycogen availability and temperature regulation in humans. J Appl Physiol. 1989;66(1):72-78.
4. Neufer PD, Young AJ, Sawka MN, Muza SR. Influence of skeletal muscle glycogen on passive rewarming after hypothermia. J Appl Physiol ;65(2):
5. Young AJ, Sawka MN, Neufer PD, Muza SR, Askew EW, Pandolf KB. Thermoregulation during cold water immersion is unimpaired by low muscle glycogen levels. J Appl Physiol. 1989;66(4):
6. Haman F, Peronnet F, Kenny GP, et al. Effects of carbohydrate availability on sustained shivering I. Oxidation of plasma glucose, muscle glycogen, and proteins. J Appl Physiol. 2004;96(1):32-40.