Differential changes in appetite hormones post-prandially based on menstrual cycle phase and oral contraceptive use: A preliminary study.

This was a preliminary study that examined whether appetite regulation is altered during the menstrual cycle or with oral contraceptives. Ten naturally cycling females (NON-USERS) and nine tri-phasic oral contraceptive using females (USERS) completed experimental sessions during each menstrual phase (follicular phase: FP; ovulatory phase: OP; luteal phase: LP). Appetite perceptions and blood samples were obtained fasted, 30, 60, and 90 min post-prandial to measure acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and total peptide tyrosine tyrosine (PYY). Changes were considered important if p < 0.100 and the effect size was ≥medium. There appeared to be a three-way (group x phase x time) interaction for acylated ghrelin where concentrations appeared to be greater in USERS versus NON-USERS during the OP 90-min post-prandial and during the LP fasted, and 90-min post-prandial. In USERS, ghrelin appeared to be greater 90-min post-prandial in the OP versus the FP with no other apparent differences between phases. There were no apparent differences between phases in NON-USERS. There appeared to be a three-way interaction for PYY where concentrations appeared to be greater in USERS during the FP 60-min post-prandial and during the OP 30-min post-prandial. In USERS PYY appeared to be greater 60-min post-prandial during the OP versus the LP with no other apparent differences. There were no apparent differences between phases in NON-USERS. There appeared to be no effect of group or phase on GLP-1, or appetite perceptions. These data demonstrate small effects of menstrual cycle phase and oral contraceptive use on the acylated ghrelin and total PYY response to a standardized meal, with no effects on active GLP-1 or perceived appetite, though more work with a large sample size is necessary.

Topical application of the pharmacological cold mimetic menthol stimulates brown adipose tissue thermogenesis through a TRPM8, UCP1, and norepinephrine dependent mechanism in mice housed at thermoneutrality.

Increasing whole-body energy expenditure via the pharmacological activation of uncoupling protein 1 (UCP1)-dependent brown adipose tissue (BAT) thermogenesis is a promising weight management strategy, yet most therapeutics studied in rodents to date either induce compensatory increases in energy intake, have thermogenic effects that are confounded by sub-thermoneutral housing temperatures or are not well tolerated in humans. Here, we sought to determine whether the non-invasive topical application of the pharmacological cold mimetic and transient receptor potential (TRP) cation channel subfamily M member 8 (TRPM8) agonist L-menthol (MNTH), could be used to stimulate BAT thermogenesis and attenuate weight gain in mice housed at thermoneutrality. Using three different strains of mice and multiple complimentary approaches to quantify thermogenesis in vivo, coupled with ex vivo models to quantify direct thermogenic effects, we were able to convincingly demonstrate the following: (1) acute topical MNTH application induces BAT thermogenesis in a TRPM8- and UCP1-dependent manner; (2) MNTH-induced BAT thermogenesis is sufficient to attenuate weight gain over time without affecting energy intake in lean and obese mice; (3) the ability of topical MNTH application to stimulate BAT thermogenesis is mediated, in part, by a central mechanism involving the release of norepinephrine. These data collectively suggest that topical application of MNTH may be a promising weight management strategy.

Fasting or the short-term consumption of a ketogenic diet protects against antipsychotic-induced hyperglycaemia in mice.

Antipsychotic (AP) medications, such as olanzapine (OLZ), are used in the treatment of schizophrenia and a growing number of 'off-label' conditions. A single dose of OLZ causes robust increases in blood glucose within minutes of treatment. The purpose of the current study was to investigate whether interventions that increase circulating ketone bodies (fasting, ß-hydroxybutyrate (ßHB), ketone esters or a ketogenic diet (KD)) would be sufficient to protect against the acute metabolic side effects of OLZ. We demonstrate that fasting or the short-term consumption of a KD protects against OLZ-induced hyperglycaemia, independent of alterations in whole-body insulin action, and in parallel with a blunted rise in serum glucagon. Interestingly, the effects of fasting and KDs were not recapitulated by acutely increasing circulating concentrations of ketone bodies through treatment with ßHB or oral ketone esters, approaches which increase ketone bodies to physiological or supra-physiological levels, respectively. Collectively, our findings demonstrate that fasting and the short-term consumption of a KD can protect against acute AP-induced perturbations in glucose homeostasis, whereas manipulations which acutely increase circulating ketone bodies do not elicit the same beneficial effects. KEY POINTS: Antipsychotic medications cause rapid and robust increases in blood glucose. Co-treatment approaches to offset these harmful metabolic side effects have not been identified. We demonstrate that fasting or the consumption of a short-term ketogenic diet, but not treatment with ß-hydroxybutyrate or oral ketone esters, protects against acute antipsychotic-induced hyperglycaemia. The protective effects of fasting and ketogenic diets were paralleled by reductions in serum glucagon, but not improvements in whole-body insulin action.

Intermittent cold exposure improves glucose homeostasis despite exacerbating diet-induced obesity in mice housed at thermoneutrality.

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. ABSTRACT: 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.

The confounding effects of sub-thermoneutral housing temperatures on aerobic exercise-induced adaptations in mouse subcutaneous white adipose tissue.

Mice are the most commonly used model organism for human biology, and failure to acknowledge fundamental differences in thermal biology between these species has confounded the study of adipose tissue metabolism in mice and its translational relevance to humans. Here, using exercise biochemistry as an example, we highlight the subtle yet detrimental effects sub-thermoneutral housing temperatures can have on the study of adipose tissue metabolism in mice. We encourage academics and publishers to consider ambient housing temperature as a key determinant in the methodological conception and reporting of all research on rodent white adipose tissue metabolism.

Biochemical adaptations in white adipose tissue following aerobic exercise: from mitochondrial biogenesis to browning.

Our understanding of white adipose tissue (WAT) biochemistry has evolved over the last few decades and it is now clear that WAT is not simply a site of energy storage, but rather a pliable endocrine organ demonstrating dynamic responsiveness to the effects of aerobic exercise. Similar to its established effects in skeletal muscle, aerobic exercise induces many biochemical adaptations in WAT including mitochondrial biogenesis and browning. While past research has focused on the regulation of these biochemical processes, there has been renewed interest as of late given the potential of harnessing WAT mitochondrial biogenesis and browning to treat obesity and type II diabetes. Unfortunately, despite increasing evidence that innumerable factors, both exercise induced and pharmacological, can elicit these biochemical adaptations in WAT, the underlying mechanisms remain poorly defined. Here, we begin with a historical account of our understanding of WAT exercise biochemistry before presenting detailed evidence in favour of an up-to-date model by which aerobic exercise induces mitochondrial biogenesis and browning in WAT. Specifically, we discuss how aerobic exercise induces increases in WAT lipolysis and re-esterification and how this could be a trigger that activates the cellular energy sensor 5' AMP-activated protein kinase to mediate the induction of mitochondrial biogenesis and browning via the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator-1 alpha. While this review primarily focuses on mechanistic results from rodent studies special attention is given to the translation of these results, or lack thereof, to human physiology.

Individual patterns of response to traditional and modified sprint interval training.

We compared the incidence of response between a traditional sprint interval training (SIT) protocol (30:240: 4-6 x 30-s, 240-s recovery) and 2 modified SIT protocols (15:120: 8-12 x 15-s, 120-s recovery; 5:40: 24-36 x 5-s, 40-s recovery) over 4 weeks of training in 84 recreationally active individuals (n = 23 per SIT group/15 control participants). Pre- and post-testing measures included V. O2max, 5-km time trial, and anaerobic capacity. Responders were classified using 2x typical error and seven other approaches to explore the impact of classification method on response rates. There was no difference in the proportion (2x typical error) of V.O2max responders across groups (30:240: 64%; 15:120: 39%; 5:40: 41%; CTRL: 33%; P= 0.190). The 30:240 group had more responders (P< 0.05) for time trial performance (70%) and peak speed during the 30 s running test (48%) compared to CTRL (21% and 0%, respectively). There were no other between-group differences (P> 0.112). Approaches with the largest response thresholds resulted in the fewest responders highlighting response rates are influenced by the method used. Additionally, we observed intra-individual differences in responsiveness across outcomes. This is the first study to empirically test the difference in the incidence of response and demonstrate individual patterns of response across different SIT protocols.

Housing temperature affects the acute and chronic metabolic adaptations to exercise in mice.

KEY POINTS: Mice are commonly housed at room temperatures below their thermoneutral zone meaning they are exposed to chronic thermal stress. Endurance exercise induces browning and mitochondrial biogenesis in white adipose tissue of rodents, but there are conflicting reports of this phenomenon in humans. We hypothesized that the ambient room temperature at which mice are housed could partially explain these discrepant reports between humans and rodents. We housed mice at room temperature or thermoneutrality and studied their physiological responses to acute and chronic exercise. We found that thermoneutral housing altered running behaviour and glucose homeostasis, and further, that exercise-induced markers of mitochondrial biogenesis and the browning of white adipose tissue were reduced in mice housed at thermoneutrality. ABSTRACT: Mice are often housed at temperatures below their thermoneutral zone resulting in compensatory increases in thermogenesis. Despite this, many studies report housing mice at room temperature (RT), likely for the convenience of the researchers studying them. As such, the conflicting reports between humans and rodents regarding the ability of exercise to increase mitochondrial and thermogenic markers in white adipose tissue may be explained by the often-overlooked variable, housing temperature. To test this hypothesis, we housed male C57BL/6 mice at RT (22°C) or thermoneutrality (TN) (29°C) with or without access to a voluntary running wheel for 6 weeks or subjected them to an acute exhaustive bout of treadmill running. We examined the gene expression and protein content of select mitochondrial and thermogenic markers in skeletal muscle, epididymal white adipose tissue (eWAT), inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT). We also assessed adipocyte morphology and indices of glucose homeostasis. Housing temperature influenced glucose tolerance and insulin action in vivo, yet the beneficial effects of exercise, both acute and chronic, remained intact in eWAT, BAT and skeletal muscle irrespective of housing temperature. Housing mice at TN led to an attenuation of some of the effects of exercise on iWAT. Collectively, we present data characterizing the acute and chronic metabolic adaptations to exercise at different housing temperatures and demonstrate, for the first time, that temperature influences the ability of exercise to increase markers of mitochondrial biogenesis and the browning of white adipose tissue.

Salsalate and/or metformin therapy confer beneficial metabolic effects in olanzapine treated female mice.

Antipsychotic medications are used in the management of schizophrenia and a growing number of off-label conditions. While effective at reducing psychoses, these drugs possess noted metabolic side effects including weight gain, liver lipid accumulation and disturbances in glucose and lipid metabolism. To counter the side effects of antipsychotics standard of care has typically included metformin. Unfortunately, metformin does not protect against antipsychotic induced metabolic disturbances in all patients and thus additional treatment approaches are needed. One potential candidate could be salsalate, the prodrug of salicylate, which acts synergistically with metformin to improve indices of glucose and lipid metabolism in obese mice. The purpose of the current investigation was to compare the effects of salsalate, metformin and a combination of both drugs, on weight gain and indices of metabolic health in female mice treated with the antipsychotic, olanzapine. Herein we demonstrate that salsalate was equally as effective as metformin in protecting against olanzapine induced weight gain and liver lipid accumulation with no additional benefit of combining both drugs. Conversely, metformin treatment, either alone or in combination with salsalate, improved indices of glucose metabolism and increased energy expenditure in olanzapine treated mice. Collectively, our findings provide evidence that dual therapy with both metformin and salsalate could be an efficacious approach with which to dampen the metabolic consequences of antipsychotic medications.

Interleukin-6 is not involved in appetite regulation following moderate-intensity exercise in males with normal weight and obesity.

OBJECTIVE: In obesogenic states and after exercise, interleukin (IL)-6 elevations are established, and IL-6 is speculated to be an appetite-regulating mechanism. This study examined the role of IL-6 on exercise-induced appetite regulation in sedentary normal weight (NW) males and those with obesity (OB). METHODS: Nine NW participants and eight participants with OB completed one non-exercise control (CTRL) and one moderate-intensity continuous training (MICT; 60 minutes, 65% V̇O2max ) session. IL-6, acylated ghrelin, active peptide tyrosine-tyrosine3-36 , active glucagon-like peptide-1, and overall appetite perceptions were measured fasted, pre exercise, and 30, 90, and 150 minutes post exercise. RESULTS: Fasted IL-6 concentrations were elevated in OB (p = 0.005, η p 2 = 0.419); however, increases following exercise were similar between groups (p = 0.934, η p 2 = 0.000). Acylated ghrelin was lower in OB versus NW (p < 0.017, d > 0.84), and OB did not respond to MICT (p > 0.512, d < 0.44) although NW had a decrease versus CTRL (p < 0.034, d > 0.61). IL-6 did not moderate/mediate acylated ghrelin release after exercise (p > 0.251). There were no observable effects of MICT on tyrosine-tyrosine3-36 , glucagon-like peptide-1, or overall appetite (p > 0.334, η p 2 < 0.062). CONCLUSIONS: These results suggest that IL-6 is not involved in exercise-induced appetite suppression. Despite blunted appetite-regulatory peptide responses to MICT in participants with OB, NW participants exhibited decreased acylated ghrelin; however, no differences in appetite perceptions existed between CTRL and MICT or NW and OB.

Enhancing endogenous levels of GLP1 dampens acute olanzapine induced perturbations in lipid and glucose metabolism.

Olanzapine is a second-generation antipsychotic (SGA) used in the treatment of schizophrenia and several on- and off-label conditions. While effective in reducing psychoses, acute olanzapine treatment causes rapid hyperglycemia, insulin resistance, and dyslipidemia and these perturbations are linked to an increased risk of developing cardiometabolic disease. Pharmacological agonists of the glucagon-like peptide-1 (GLP1) receptor have been shown to offset weight-gain associated with chronic SGA administration and mitigate the acute metabolic side effects of SGAs. The purpose of this study was to determine if increasing endogenous GLP1 is sufficient to protect against acute olanzapine-induced impairments in glucose and lipid homeostasis. Male C57BL/6J mice were treated with olanzapine, in the absence or presence of an oral glucose tolerance test (OGTT), and a combination of compounds to increase endogenous GLP1. These include the non-nutritive sweetener allulose which acts to induce GLP1 secretion but not other incretins, the DPPiv inhibitor sitagliptin which prevents degradation of active GLP1, and an SSTR5 antagonist which relieves inhibition on GLP1 secretion. We hypothesized that this cocktail of agents would increase circulating GLP1 to supraphysiological concentrations and would protect against olanzapine-induced perturbations in glucose and lipid homeostasis. We found that 'triple treatment' increased both active and total GLP1 and protected against olanzapine-induced perturbations in lipid and glucose metabolism under glucose stimulated conditions and this was paralleled by an attenuation in the olanzapine induced increase in the glucagon:insulin ratio. Our findings provide evidence that pharmacological approaches to increase endogenous GLP1 could be a useful adjunct approach to reduce acute olanzapine-induced perturbations in lipid and glucose metabolism.

Liver triacylglycerol accumulation but not postprandial lipemia is reduced by a skim milk powder diet in male rats.

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.

The glucose lowering effects of CL 316,243 dissipate with repeated use and are rescued bycilostamide.

Repeated activation of the beta 3 adrenergic receptor (ß3AR) with the agonist CL 316,243 (CL) results in remodeling of white adipose tissue (WAT) characterized by increased mitochondrial enzymes and expression of uncoupling protein 1 (UCP1). ß3AR activation also has profound acute metabolic effects including rapidly decreasing blood glucose, secondary to fatty acid-induced increases in insulin, and increasing energy expenditure. The acute (single dose) effects of ß3AR activation have largely been examined in treatment naive animals and under room temperature housing conditions. The current study examined if repeated CL treatment would lead to an attenuation of acute metabolic effects of CL treatment under thermoneutral housing conditions and if this could be rescued with cilostamide, a phosphodiesterase inhibitor. We provide evidence demonstrating that the acute effects of CL to increase serum fatty acids and insulin and reduce blood glucose, but not increases in energy expenditure, are attenuated in mice following repeated treatment with CL. This occurs in parallel with reductions in indices of protein kinase A signaling in WAT including the phosphorylation of hormone sensitive lipase. The findings of attenuated serum fatty acid, insulin, and blood glucose responses were confirmed in both high-fat fed and UCP1-/- mice repeatedly treated with CL. Desensitization to CL in mice was rescued by cilostamide. Herein, we provide evidence that the glucose lowering, but not thermogenesis inducing, effects of CL are attenuated with repeated treatment and can be rescued by cilostamide. The findings of this study point toward novel adjunct treatment approaches that could be used to maximize therapeutic, glucose lowering effects of ß3AR agonists.

Voluntary physical activity protects against olanzapine-induced hyperglycemia.

Olanzapine (OLZ) is used in the treatment of schizophrenia and a growing number of "off-label" conditions. Although effective in reducing psychoses, OLZ causes rapid impairments in glucose and lipid homeostasis. The purpose of this study was to investigate if voluntary physical activity via wheel running (VWR) would protect against the acute metabolic side effects of OLZ. Male C57BL/6J mice remained sedentary or were provided with running wheels overnight, before treatment with OLZ either at the beginning of the light cycle, or 7 or 24 h following the cessation of VWR. Prior VWR protected against OLZ-induced hyperglycemia immediately and 7 h following a bout of overnight wheel running. Protection against, hyperglycemia immediately following VWR was associated with increased insulin tolerance and an attenuated OLZ-induced increase in the serum glucagon:insulin ratio. The protective effect of VWR against OLZ-induced increases in hyperglycemia and glucagon:insulin ratio was maintained in high-fat fed, and AMPK ß1-deficient mice, models which display a potentiated OLZ-induced increase in blood glucose. Repeated OLZ treatment did not impair VWR performance and protection against the acute effects of OLZ on blood glucose was present after 1 wk of daily OLZ treatment in mice given access to running wheels. In contrast to the effects on glucose metabolism, VWR, for the most part, did not impact OLZ-induced perturbations in lipolysis, liver triglyceride accumulation, or whole body substrate oxidation. Collectively, our findings demonstrate the efficacy of voluntary physical activity as an approach to protect against OLZ-induced impairments in glucose metabolism.NEW & NOTEWORTHY The antipsychotic medication olanzapine causes rapid and large increases in blood glucose. We demonstrate that a prior bout of voluntary overnight wheel running can protect against this harmful side effect and is likely mediated by reductions in olanzapine-induced increases in the circulating glucagon to insulin ratio. This study highlights the powerful effects of voluntary activity in conditions of treatment with antipsychotic medications.

Greater lactate accumulation following an acute bout of high-intensity exercise in males suppresses acylated ghrelin and appetite postexercise.

High-intensity exercise inhibits appetite, in part, via alterations in the peripheral concentrations of the appetite-regulating hormones acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and active peptide tyrosine-tyrosine (PYY). Given lactate may mediate these effects, we used sodium bicarbonate (NaHCO3) supplementation in a double-blind, placebo-controlled, crossover design to investigate lactate's purported role in exercise-induced appetite suppression. Eleven males completed two identical high-intensity interval training sessions (10 × 1 min cycling bouts at ~90% heart rate maximum interspersed with 1-min recovery), where they ingested either NaHCO3 (BICARB) or sodium chloride (NaCl) as a placebo (PLACEBO) preexercise. Blood lactate, acylated ghrelin, GLP-1, and PYY concentrations, as well as overall appetite were assessed preexercise and 0, 30, 60, and 90 min postexercise. Blood lactate was greater immediately (P < 0.001) and 30 min postexercise (P = 0.049) in the BICARB session with an increased (P = 0.009) area under the curve (AUC). The BICARB session had lower acylated ghrelin at 60 (P = 0.014) and 90 min postexercise (P = 0.016), with a decreased AUC (P = 0.039). The BICARB session had increased PYY (P = 0.034) with an increased AUC (P = 0.031). The BICARB session also tended (P = 0.060) to have increased GLP-1 at 30 (P = 0.003) and 60 min postexercise (P < 0.001), with an increased AUC (P = 0.030). The BICARB session tended (P = 0.059) to reduce overall appetite, although there was no difference in AUC (P = 0.149). These findings support a potential role for lactate in the high-intensity exercise-induced appetite-suppression.NEW & NOTEWORTHY We used sodium bicarbonate to increase lactate accumulation or sodium chloride as a placebo. Our findings further implicate lactate as a mediator of exercise-induced appetite suppression, given exercise-induced increases in lactate during the sodium bicarbonate session altered peripheral concentrations of appetite-regulating hormones, culminating in a reduction of appetite. This supports a lactate-dependent mechanism of appetite suppression following high-intensity exercise and highlights the potential of using lactate as a means of inducing a caloric deficit.

Epinephrine responsiveness is reduced in livers from trained mice.

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.

High Load With Lower Repetitions vs. Low Load With Higher Repetitions: The Impact on Asymmetry in Weight Distribution During Deadlifting.

This study investigated weight distribution between the lower limbs using a symmetry index (SI) score of the vertical ground reaction forces (GRF) and measures of postural stability in high load/low repetition (termed "heavy") and low load/high repetition (termed "light") deadlifting. Ten participants performed two deadlift protocols with equal cumulative external load. These protocols were designed to represent standard high load/low repetition and low load/high repetition workouts; order was random and separated by 7 days. An effect of lifting condition (p = 0.023) and set number (p = 0.011) was observed such that lifts in the heavy condition were less symmetrical than those in the light condition and lifts became more symmetrical as set number increased. There was no effect of lift number on symmetry of force production (p = 0.127). Additional analysis revealed that center of pressure (COP) path length was greater during heavy lifts (p = 0.002) however COP range was unaffected suggesting controlled point of force application within the same boundaries regardless of lifting condition. As asymmetries have been previously associated with increased injury risk, greater training emphasis on the symmetrical performance of sub-maximal deadlifts should be considered to try to minimize the development of asymmetries.

The effects of a pre-exercise meal on postexercise metabolism following a session of sprint interval training.

Sprint interval training (SIT) has demonstrated reductions in fat mass through potential alterations in postexercise metabolism. This study examined whether exercising in the fasted or fed state affects postexercise metabolism following acute SIT. Ten active males performed a bout of modified SIT (8 × 15-s sprints; 120 s recovery) in both a fasted (FAST) and fed (FED) state. Gas exchange was collected through 3 h postexercise, appetite perceptions were measured using a visual analog scale, and energy intake was recorded using dietary food logs. There was no difference in energy expenditure between conditions at any time point (p > 0.329) or in total session energy expenditure (FED: 514.8 ± 54.9 kcal, FAST: 504.0 ± 74.3 kcal; p = 0.982). Fat oxidation at 3 h after exercise was higher in FED (0.110 ± 0.04 g·min-1) versus FAST (0.069 ± 0.02 g·min-1; p = 0.013) though not different between conditions across time (p > 0.340) or in total postexercise fat oxidation (FED: 0.125 ± 0.04 g·min-1, FAST: 0.105 ± 0.02 g·min-1; p = 0.154). Appetite perceptions were lower in FED (-4815.0 ± 4098.7 mm) versus FAST (-707.5 ± 2010.4 mm, p = 0.022); however, energy intake did not differ between conditions (p = 0.429). These results demonstrate the fasted or fed state does not augment postexercise metabolism following acute SIT in a way that would favour fat loss following training. Novelty Energy expenditure was similar between conditions, while fat oxidation was significantly greater in FED at 3 h after exercise. Appetite perceptions were significantly lower in FED; however, energy intake was not different between conditions. Current findings suggest that performing SIT in the fed or fasted state would not affect fat loss following training.