Prior exercise training improves cold tolerance independent of indices associated with non‐shivering thermogenesis

Abstract

Shivering is one of the first defences against cold, and as skeletal muscle fatigues there is an increased reliance on non-shivering thermogenesis. Brown and beige adipose tissues are the primary thermogenic tissues regulating this process. Exercise has also been shown to increase the thermogenic capacity of subcutaneous white adipose tissue. Whether exercise has an effect on the adaptations to cold stress within adipose tissue and skeletal muscle remains to be shown. Male C57BL/6 mice were either subjected to voluntary wheel running or remained sedentary for 12 days. Exercise led to decreased body weight and increased glucose tolerance. Mice were then divided into groups kept at 25°C room temperature or a cold challenge of 4°C for 48 h. Exercised mice were protected against cold-induced reductions in weight and in parallel with increased food intake. Providing exercised mice with the same amount of food as sedentary mice eliminated the protection against cold-induced weight loss. Cold exposure led to greater reductions in rectal temperature in sedentary compared to exercised mice. This protective effect was not explained by differences in the browning of white adipose tissue or brown adipose tissue mass. Similarly, the ability of the β -adrenergic agonist CL 316,243 to increase energy expenditure was attenuated in previously exercised mice, suggesting that the activation of uncoupling protein-1 in brown and/or beige adipocytes is not the source of protective effects. We speculate that the protection against cold-induced reductions in rectal temperature could potentially be linked to exercise-induced alterations in skeletal muscle.

Epinephrine responsiveness is reduced in livers from trained mice

“…SED mice remained individually housed in standard shoebox cages while TR mice were moved to individual cages with running wheels and wired bike computers (M3.1 WR VDO Cycle Computing) to track distance and speed. TR mice had access to wheels for 12 days, a length chosen based off previous work that demonstrated significant metabolic adaptations with this 12‐day voluntary wheel running (VWR) protocol (Knuth et al, ). Food intake, body weight, running distance and running time were recorded every other day for all mice.…”

Loss of glucagon signaling alters white adipose tissue browning

“…At ∼9:00 am , all mice were weighed, blood glucose was measured, body temperature was assessed using a rectal thermometer (TH‐5 Thermalert Monitoring System; Physitemp, Clifton, NJ, USA), and mice were either placed at 4°C for 48 h or remained at room temperature (25°C) (we recognize that 48 h is relatively short for cold exposure, but we could not obtain ethics for longer exposures). Mice were housed individually in shoebox cages with corncob bedding and no environmental enrichment but free access to standard chow (Teklad 7004; Envigo, Somerset, NJ, USA) and water, as we have previously described (4). Body weight, body temperature, blood glucose, and food intake were assessed at 6, 12, 24, 36, and 48 h during cold exposure (4).…”

“…Mice were housed individually in shoebox cages with corncob bedding and no environmental enrichment but free access to standard chow (Teklad 7004; Envigo, Somerset, NJ, USA) and water, as we have previously described (4). Body weight, body temperature, blood glucose, and food intake were assessed at 6, 12, 24, 36, and 48 h during cold exposure (4). Immediately after 48 h (9:00 am ), mice were anesthetized by an intraperitoneal injection of sodium pentobarbital (∼60 mg/kg).…”

“…Membranes were briefly washed in TBST and incubated for 1 h at room temperature with horseradish peroxidase–conjugated secondary antibodies (1:2000), and signals were detected using chemiluminescence. Protein content was expressed relative to a within‐gel Ponceau stain loading control (1, 4, 24). Primary antibodies were purchased from Abeam (Cambridge, United Kingdom) for UCP‐1 (0983) and oxidative phosphorylation (oxphos) cocktail (110413), MilliporeSigma for PGC1‐α (AB3242), and Cell Signaling Technology (Danvers, MA, USA) for total PKB (9272), phosphorylated (p)PKB Ser473 (9271), total ATGL (2138) pATGL ser406 (2439), total HSL (4107), pHSL Ser563 (4139), GAPDH (2118), and PKA substrates (9624).…”

“…A great deal of research has attempted to understand the mechanisms behind WAT browning and has identified various endocrine factors that appear to contribute (6, 9, 10). Glucagon has been largely ignored when it comes to adipose tissue metabolism even though the glucagon receptor is present in both eWAT and interscapular BAT (11), and physiologic challenges that cause WAT browning, such as cold exposure (7, 9) and exercise (1, 2, 4), are associated with increased circulating glucagon (12–14). Moreover, glucagon can increase whole‐body energy expenditure (EE) (15) and stimulate blood flow and heat production in rodent BAT (16, 17).…”