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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. [ABSTRACT FROM AUTHOR]

Increases in postprandial lipids are linked to the development of cardiometabolic and fatty liver disease. Prior work has suggested that dairy possesses beneficial cardiometabolic effects and thus the aim of the current investigation was to test the hypotheses that the habitual consumption of dairy, in the form of skim milk powder (SMP), would protect against increases in circulating lipids and liver lipid accumulation following an oral fat challenge in rats. Male rats were fed either a semipurified low-fat control diet with casein or a diet with an equivalent amount of protein (∼13% kcal) provided through skim milk powder (SMP) for 6 weeks (n = 40/group). Rats were then given an oral gavage of palm oil (5 mL/kg body weight) or an equivalent volume of water, and serum and liver were harvested 90 minutes or 4 hours after. Rats fed the SMP diet gained less weight than controls but there were no differences in glucose tolerance between groups. The fat gavage increased serum lipids in both diet groups, whereas there was a main effect of the fat challenge to increase, and the SMP diet, to decrease liver triacylglycerol accumulation. The percentage of saturated and monounsaturated fatty acids and the protein content/activity of lipogenic enzymes were reduced in livers from SMP-fed rats, whereas the percentage of polyunsaturated fatty acids was increased. In summary, we provide evidence that SMP consumption, although not protecting against postprandial lipemia, markedly attenuates triacylglycerol accumulation and the relative amount of saturated and monounsaturated fatty acids in the liver. An SMP diet reduces liver TAG accumulation and the relative percentage of saturated fatty and monounsaturated fatty acids while having no effect on indices of circulating postprandial lipemia such as TAGs, glycerol, and nonesterified fatty acids. Abbreviations: MFA, monosaturated fatty acids; NEFA, nonesterified fatty acids; PUFAs, polyunsaturated fatty acids; SFA, saturated fatty acids; SMP, skim milk powder; TAG; triacylglycerol. Biorender was used for the generation of the graphic. [Display omitted] [ABSTRACT FROM AUTHOR]

Key points: Ambient cold exposure is often regarded as a promising anti‐obesity treatment in mice.However, most preclinical studies aimed at treating obesity via cold‐induced thermogenesis have been confounded by subthermoneutral housing temperatures. Therefore, the ability of ambient cold to combat diet‐induced obesity in mice housed under humanized thermoneutral conditions is currently unknown.Moreover, mammals such as mice are rarely exposed to chronic ambient cold without reprieve, yet mice are often subjected to experimental conditions of chronic rather than intermittent cold exposure (ICE), despite ICE being more physiologically relevant.In the present study, we provide novel evidence that thermoneutral housing uncouples the effects of ICE on glucose and energy homeostasis suggesting that ICE, despite improving glucose tolerance, is not an effective obesity treatment when mice are housed under humanized thermoneutral conditions. The present study examines whether a physiologically relevant model of ambient cold exposure, intermittent cold exposure (ICE), could ameliorate the metabolic impairments of diet‐induced obesity in male and female mice housed under humanized thermoneutral conditions. Male and female C57BL/6J mice housed at thermoneutrality (29°C) were fed a low‐fat diet or high‐fat diet for 6 weeks before being weight matched into groups that remained unperturbed or underwent ICE for 4 weeks (4°C for 60 min day–1; 5 days week–1) when being maintained on their respective diets. ICE induced rapid and persistent hyperphagia exacerbating rather than attenuating high‐fat diet‐induced obesity over time. These ICE‐induced increases in adiposity were found to be energy intake‐dependent via pair‐feeding. Despite exacerbating high‐fat diet‐induced obesity, ICE improved glucose tolerance, independent of diet, in a sex‐specific manner. The effects of ICE on glucose tolerance were not attributed to improvements in whole‐body insulin tolerance, tissue specific insulin action, nor differences in markers of hepatic insulin clearance or pancreatic beta cell proliferation. 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. These data suggest that ICE, despite improving glucose tolerance, is not an effective obesity treatment in mice housed under humanized conditions. [ABSTRACT FROM AUTHOR]

R2873 --> 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. [ABSTRACT FROM AUTHOR]