Partitioning oxidative fuels during cold exposure in humans: muscle glycogen becomes dominant as shivering intensifies

Abstract

The effects of changes in shivering intensity on the relative contributions of plasma glucose, muscle glycogen, lipids and proteins to total heat production are unclear in humans. The goals of this study were: (1) to determine whether plasma glucose starts playing a more prominent role as shivering intensifies, (2) to quantify overall changes in fuel use in relation to the severity of cold exposure, and (3) to establish whether the fuel selection pattern of shivering is different from the classic fuel selection pattern of exercise. Using a combination of indirect calorimetry and stable isotope methodology, fuel metabolism was monitored in non-acclimatized adult men exposed for 90 mins to 10• C (low-intensity shivering (L)) or 5• C (moderate-intensity shivering (M)). Results show that plasma glucose oxidation is strongly stimulated by moderate shivering (+122% from L to M), but the relative contribution of this pathway to total heat generation always remains minor (< 15% of total heat production). Instead, muscle glycogen is responsible for most of the increase in heat production between L and M. By itself, the increase in CHO oxidation is responsible for the 100 W increase in metabolic rate observed between L and M, because rates of lipid and protein oxidation remain constant. This high reliance on CHO is not compatible with the well known fuel selection pattern of exercise, when considering the relatively low metabolic rates elicited by shivering (∼30%V O 2 max for M). We conclude that shivering and exercise of similar energy requirements appear to be supported by different fuel mixtures. Investigating the physiological mechanisms underlying why a muscle producing only heat (shivering), or significant movement (exercise), shows a different pattern of fuel selection at the same power output strikes us as a fascinating area for future research. In humans exposed to cold, carbohydrates (CHO) can provide up to 60% of all the heat generated (Haman et al. 2002), and two separate sources of CHO are available for thermogenesis: muscle glycogen and plasma glucose. During low-intensity shivering, we have recently shown that muscle glycogen is the dominant source of CHO, providing at least 3 times more glucosyl units than plasma glucose (Haman et al. 2002). The importance of plasma glucose also remains minor when the size of glycogen stores is experimentally increased or decreased (Haman et al. 2004c). However, indirect evidence suggests that circulating glucose may start playing a more important role at the higher metabolic rates necessary to survive during more extreme cold exposure. Using a continuous infusion of labelled glucose, Tipton et al. (1997) showed that the rate of disappearance (R d,Glu ) increases by as much as 2-fold between lowand moderate-intensity shivering. However, the exact fate of glucose leaving the circulation is still unclear because R d,Glu measurements cannot discriminate between oxidative and non-oxidative disposal. A large increase in plasma glucose utilization would not be surprising becaus...

Shivering in the cold: from mechanisms of fuel selection to survival

“…In fact, failing to account for the oxidation of proteins in the total energy budget may result in a significant overestimation of CHO and lipid oxidation rates. It is generally accepted that absolute rates of protein oxidation remain unaffected by cold exposure, and in effect, the cold-induced increases in metabolic rate is generally accompanied by a proportional decrease in the relative use of this fuel (10,12). Consequently, when protein oxidation rate is high before cold exposure, the relative importance of this fuel to total heat production remains elevated during shivering.…”

“…Although this could be true during low-intensity shivering, it is still unclear whether this would also be the case at higher shivering intensities. Important increases in the use of muscle glycogen reserves have been found as shivering intensifies (12). Clearly, additional research is needed to determine whether the selection of a specific fuel mixture affects survival time at higher shivering intensities.…”

“…To date, no evidence indicates that shivering alone can elicit hypoglycemia. In humans, plasma glucose oxidation rates always remains minor during shivering (10 -15% Ḣ prod ) (12). In addition, glycemia has even been shown to increase by ϳ10% during intense cold exposure (average of 3-4 h at 60 -70% peak shivering) (31).…”

“…Under such conditions, survival time depends on shivering endurance or on the amount of time a specific thermogenic rate can be maintained (31). Over the years, shivering studies have focused on muscle glycogen depletion as a possible limiting factor for heat production because 1) CHO represent such a small fraction of total energy stores, 2) muscle glycogen contributes as much as 30 -40% Ḣ prod of the total energy budget during shivering (12), and 3) this fuel is well known to be limiting during endurance exercise. Consequently, finding the right fuel mix and/or muscle fiber recruitment to optimize heat production and spare glycogen reserves may be critical for long-term survival in cold environments.…”

Effects of ingesting [13C]glucose early or late into cold exposure on substrate utilization

“…Partitioning of glucose utilization. During the baseline period before cold exposure, rates of plasma and muscle glucose oxidation were quantified by repeated [ 13 C]glucose ingestion (11,13,14). For this purpose, 5 g of corn-derived glucose [Ϫ11.03‰ difference (␦) 13 C vs. Vienna Pee Dee Belemnitella (V-PDB)] was further enriched with [U-13 C]glucose ( 13 C/C Ͼ 99%, Isotec, Miamisburg, OH) to obtain a final isotopic composition of ϩ200‰␦ 13 C V-PDB.…”