support-information-section).

The liver is the primary metabolic organ involved in the endogenous production of glucose through glycogenolysis and gluconeogenesis. Hepatic glucose production (HGP) is increased via neural‐hormonal mechanisms such as increases in catecholamines. To date, the effects of prior exercise training on the hepatic response to epinephrine have not been fully elucidated. To examine the role of epinephrine signaling on indices of HGP in trained mice, male C57BL/6 mice were either subjected to 12 days of voluntary wheel running or remained sedentary. Epinephrine, or vehicle control, was injected intraperitoneally on day 12 prior to sacrifice with blood glucose being measured 15 min postinjection. Epinephrine caused a larger glucose response in sedentary mice and this was paralleled by a greater reduction in liver glycogen in sedentary compared to trained mice. There was a main effect of epinephrine to increase the phosphorylation of protein kinase‐A (p‐PKA) substrates in the liver, which was driven by increases in the sedentary, but not trained, mice. Similarly, epinephrine‐induced increases in the mRNA expression of hepatic adrenergic receptors (Adra1/2a, Adrb1), and glucose‐6‐phosphatase (G6pc) were greater in sedentary compared to trained mice. The mRNA expression of cAMP‐degrading enzymes phosphodiesterase 3B and 4B (Pde3b, Pde4b) was greater in trained compared to sedentary mice. Taken together, our data suggest that prior exercise training reduces the liver's response to epinephrine. This could be beneficial in the context of training‐induced glycogen sparing during exercise.

Growth differentiating factor-15 (GDF15) is expressed, and secreted, from a wide range of tissues and serves as a marker of cellular stress. A key transcriptional regulator of this hormone is the endoplasmic reticulum stress protein, CHOP (C/EBP Homologous Protein). Exercise increases GDF15 levels but the underlying mechanisms of this are not known. To test whether CHOP regulates GDF15 during exercise we used various models of altered ER stress. We examined the effects of acute exercise on circulating GDF15 and GDF15 mRNA expression in liver, triceps skeletal muscle, and epididymal white adipose tissue and examined the GDF15 response to acute exercise in lean and high-fat diet-induced obese mice, sedentary and exercise trained mice, and CHOP deficient mice. We found that obesity augments exercise-induced circulating GDF15 although ER stress markers were similar in lean and obese mice. Exercise-induced GDF15 was increased in trained and sedentary mice that ran at the same relative exercise intensity, despite trained mice being protected against increased markers of ER stress. Finally, exercise-induced increases in GDF15 at the tissue and whole-body level were intact in CHOP deficient mice. Together, these results provide evidence that exercise-induced GDF15 expression and secretion occurs independent of ER stress/CHOP.

The landscape of nutrition advice is vast and full of misinformation. A primary source of nutrition advice in Canada comes from the Canadian Food Guide, however, many questions remain regarding the reach and accessibility of the food guide. Specifically, is the population most likely to receive and use this information, the population that needs it the most? Are there barriers to following this guide that Health Canada has failed to address? Is there evidence supporting the efficacy of this food guide in populations at risk for nutrition misinformation or diet-related preventable diseases? This commentary reviews the past research regarding efficacy of previous food guides and highlights potential barriers preventing equal and accessible use of Canada’s Food Guide.

Catecholamines increase liver glucose production at least in part through increases in glycogenolysis and gluconeogenesis. To date, the effects of prior exercise training on the liver’s response to epinephrine, in vivo, have not been fully elucidated. To examine the role of epinephrine signaling on indices of liver glucose production in trained mice, male C57BL/6 mice were subject to either 12 days of voluntary wheel running (TR) or remained sedentary (SED). Epinephrine (0.5 mg/kg body weight), or vehicle were injected intraperitoneally following 12 days of training and tissues harvested 15 minutes post‐injection. The rise in blood glucose following epinephrine injection was significantly blunted in trained compared to sedentary mice and this was paralleled by a blunted reduction in liver glycogen in trained mice. There was a main effect of epinephrine to increase the phosphorylation of protein kinase‐A substrates (pPKAs), which was driven by increases in the sedentary, but not trained, mice. Similarly, epinephrine‐induced increases in the mRNA expression of α‐ and β‐adrenergic receptor 1 and 2 and glucose‐6‐phosphatase were greater in SED compared to TR mice. Exercise and epinephrine decreased serum insulin levels and increased glucagon levels, however, there were no differences within epinephrine treated groups. Changes in phosphorylated AKT, AMPK, and phosphodiesterase 4B protein content, negative regulators of PKA signaling, do not explain the protective effects of exercise training against epinephrine induced increases in blood glucose and liver glycogen breakdown. Taken together our data suggest that prior exercise training reduces the liver’s response to epinephrine. This could be beneficial in the context of training‐induced sparing of glycogen during exercise. Support or Funding Information This work was funded, in part, through a National Sciences and Engineering Research Council of Canada (NSERC) grant to D.C.W., who is a Tier II Canada Research Chair in Lipids, Metabolism, and Health. H.A.D was supported by an Ontario Graduate Scholarship. G.L.M. was supported by an Ontario Graduate Scholarship and subsequently an NSERC Canada Graduate Scholarship. L.K.T. was supported by a Dairy Farmers of Ontario Doctoral Research Assistantship and an NSERC Postgraduate Scholarship.

Chronic ambient cold exposure has been regarded as a promising obesity treatment given it potently increases energy expenditure. However, few mammals are chronically exposed to cold ambient conditions without reprieve highlighting the need to determine whether more physiologically relevant interventions, such as intermittent ambient cold exposure, could be utilized to treat obesity. Moreover, most preclinical cold exposure work to date has been conducted at housing temperatures below thermoneutrality, unintentionally confounding metabolic outcomes. As such, this study examined whether intermittent ambient cold exposure could abrogate the metabolic impairments of diet‐induced obesity, in mice housed under humanized thermoneutral conditions. Eight‐week‐old male and female C57Bl/6J mice (n ≥ 40/sex) were singly housed, acclimated to thermoneutrality (30 °C), and then weight matched into low‐fat (LFD; 10% kcal from fat) or high‐fat (HFD; 45% kcal from fat) diet fed groups. Male and female mice were given six weeks to feed on their respective diets before being weight‐matched into groups that remained unperturbed (CTRL) or underwent intermittent ambient cold exposure (ICE), respectively. ICE consisted of exposure to 4 °C for one hour/day, five days/week, for four weeks. Mice remained on their respective diets for the entire four‐week intervention period, during which time glucose and insulin tolerance were assessed. Following the intervention mice were sedated with sodium pentobarbital and sacrificed by exsanguination of the heart. The epididymal and inguinal white adipose tissue depots (eWAT and iWAT, respectively), the interscapular brown adipose tissue depot (BAT), as well as the liver, triceps, and hypothalamus were excised, snap‐frozen in liquid nitrogen, and stored at ‐80 °C. ICE induced hyperphagia that was rapid in onset and persistent, occurring with every exposure independent of diet. Over time, this exacerbated rather than attenuated HFD‐induced obesity in both male and female mice, increasing BAT, eWAT, and iWAT mass as well as cellular lipid deposition. Pair‐feeding revealed that these ICE‐induced increases in adiposity were energy intake dependent, as the pair‐fed, but not ad libitum fed, HFD‐ICE group was protected from ICE‐induced increases in body mass. Despite exacerbating HFD‐induced obesity, ICE improved glucose tolerance, independent of diet, in a sex‐dependent manner. The effects of ICE on glucose tolerance were not attributed to improvements in whole‐body insulin tolerance, tissue specific insulin action, nor to differences in hepatic insulin clearance. Instead, ICE increased serum concentrations of insulin and C‐peptide in response to glucose, suggesting that ICE may improve glucose tolerance by potentiating pancreatic glucose‐stimulated insulin secretion. Taken together, this data suggests that intermittent ambient cold exposure, despite improving glucose tolerance, is not an effective obesity treatment in mice housed under humanized conditions.

No abstract