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Greater lactate accumulation following an acute bout of high-intensity exercise in males suppresses acylated ghrelin and appetite post-exercise
Abstract
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 utilized sodium bicarbonate (NaHCO 3 ) 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 x 1 min cycling bouts at ~90% heart rate maximum interspersed with 1 min recovery), where they ingested either NaHCO 3 (BICARB) or sodium chloride (NaCl) as a placebo (PLACEBO) pre-exercise. Blood lactate, acylated ghrelin, GLP-1, and PYY concentrations, as well as overall appetite were assessed pre-exercise and 0, 30, 60, and 90 min post-exercise. Blood lactate was greater immediately (P<0.001) and 30 min post-exercise (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 post-exercise (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 post-exercise (P<0.001) with an increased AUC (P=0.030). The BICARB session tended (P=0.059) to reduce overall appetite, though 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.
... Incremental test protocol, gas collection, and termination/VȮ 2max criteria were as previously described [25]. After a 20-minute rest period, a verification phase to confirm V̇O 2max was completed at a constant workload (105% of the work achieved on the graded test) until 50 rpm could not be maintained [26]. ...
... Subjective appetite perceptions were measured using a visual analog scale for perceptions of hunger (i.e., "How hungry do you feel?"), fullness (i.e., "How full do you feel?"), satisfaction (i.e., "How satisfied do you feel?"), and prospective energy intake (i.e., "How much do you think you could eat?") on a 100 mm scale anchored with contrasting statements as previously validated in males [17,25,27]. An overall appetite rating was quantified as the mean value of the four appetite ratings after inverting satisfaction and fullness values [17,23,25]. ...
... Subjective appetite perceptions were measured using a visual analog scale for perceptions of hunger (i.e., "How hungry do you feel?"), fullness (i.e., "How full do you feel?"), satisfaction (i.e., "How satisfied do you feel?"), and prospective energy intake (i.e., "How much do you think you could eat?") on a 100 mm scale anchored with contrasting statements as previously validated in males [17,25,27]. An overall appetite rating was quantified as the mean value of the four appetite ratings after inverting satisfaction and fullness values [17,23,25]. ...
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 $$ {\upeta}_p^2 $$ = 0.419); however, increases following exercise were similar between groups (p = 0.934, η p 2 $$ {\upeta}_p^2 $$ = 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 $$ {\upeta}_p^2 $$ < 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.
... Although a variety of mechanisms (e.g., blood flow redistribution, sympathetic nervous system activity, gastrointestinal motility, cytokine release, free fatty acid concentrations, lactate production, and changes in plasma glucose and insulin concentrations) have been proposed to explain these effects (11), only a few of these potential mechanisms have been investigated in more detail. One potential mechanism that has gained attention is lactate (26) where human work from our laboratory (12,27) along with mechanistic research in cell and animal models (28)(29)(30)(31) provide strong support for lactate's role in appetite regulation. The proposed mechanisms (26) for lactate's role in exerciseinduced appetite suppression include lactate's ability: 1) to attenuate the release and activation of ghrelin from ghrelinproducing gastric cells (28); 2) to alter key hypothalamic signaling pathways that control neuropeptide expression/release (29,30); and 3) to inhibit ghrelin signaling through the ghrelin receptor in the hypothalamus (31). ...
... A sample size calculation was completed a priori using GPower 3.1. Using a large effect size determined from previous studies (f = 0.617) exploring differences in acylated ghrelin, active PYY, and active GLP-1 following exercise (12,27), an alpha value of 0.05, and 80% power, a sample size of eight participants was necessary to detect differences in these appetite hormone concentrations following exercise using a two-way repeated measures analysis of variance (RM ANOVA; 4 conditions, 4 time points). The sample recruited (n = 9) is similar to previous work (8-12 participants) assessing changes in appetite-regulating hormones postexercise (12-14, 16, 18-22, 25, 27, 40-42). ...
... In the 2nd tube, 10 lL of DPP-IV inhibitor and 500 KIU of aprotinin were added per milliliters of blood to prevent inactivation of GLP-1 and ex vivo conversion of PYY 1-36 to PYY . All tubes were gently inverted 10 times and centrifuged at 3,000 g for 10 min at À4 C, after which the plasma supernatant was aliquoted into Eppendorf tubes, while the plasma from the acylated ghrelin vacutainer (containing AEBSF) was acidified by the addition of 100 lL of HCl per 1 mL of plasma (12,27). All samples were stored at -80 C for subsequent analysis, whereby commercially available enzyme-linked immunosorbent assays were conducted to determine plasma concentrations of acylated ghrelin (EZGRA-88K, EMD Millipore, Burlington, MA), active GLP-1 (EZGLPHS-35K, EMD Millipore), and active PYY (EK-059-02, Phoenix Pharmaceuticals, San Diego, CA) as per manufacturer's instructions. ...
Unlabelled:
Exercise in young adults (18-25 y) suppresses appetite in a dose-response relationship with exercise intensity. While several mechanisms have been proposed to explain this response, lactate is the most well established. To date, no study has investigated this specifically in middle-aged adults where the appetite response to a meal is different.
Purpose:
To explore the effects of submaximal, near maximal, and supramaximal intensity exercise on appetite regulation in middle-aged adults.
Methods:
Nine participants (age: 45±10 y) completed 4 experimental sessions: 1) no-exercise control (CTRL); 2) moderate-intensity continuous training (MICT; 30 min, 65% V̇O2max); 3) high-intensity interval training (HIIT; 10 x 1 min efforts, 90% heart rate maximum, 1 min recovery); and 4) sprint interval training (SIT; 8 x 15 s "all-out" efforts, 2 min recovery). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), active peptide tyrosine tyrosine (PYY), lactate, and subjective appetite perceptions were measured pre-exercise, 0-, 30-, and 90-min post-exercise. Energy intake was recorded the day before and of each session.
Results:
Acylated ghrelin was suppressed (P<0.001, =0.474) by HIIT (0-min, and 30-min post-exercise; P<0.091, d>1.84) and SIT (0-min, 30-min, and 90-min post-exercise; P<0.037, d>1.72) compared to CTRL, and SIT suppressed concentrations compared to MICT (0-min, and 30-min post-exercise; P<0.91, d>1.19). There were no effects of exercise on active PYY, active GLP-1, appetite perceptions, or free-living energy intake (P>0.126, <0.200).
Conclusion:
Intense interval exercise that generates lactate accumulation suppresses acylated ghrelin with little effect on anorexigenic hormones, overall appetite, or free-living energy intake.
... However, it is clear that the arcuate nucleus of the hypothalamus is the site of hunger regulation (138,139). The gut hormone ghrelin is one of the hormones that informs the hypothalamic centers of body energy status (140,141). The suppressive effect of hard exercise on appetite (142)(143)(144) is consistent with results that lactatemia acts via suppression of ghrelin secretion (54,140). ...
... The gut hormone ghrelin is one of the hormones that informs the hypothalamic centers of body energy status (140,141). The suppressive effect of hard exercise on appetite (142)(143)(144) is consistent with results that lactatemia acts via suppression of ghrelin secretion (54,140). The ghrelin receptor [growth hormone secretagogue receptor (GHSR-1a)] is a G-protein coupled receptor expressed throughout both the stomach and GI tract. ...
No longer viewed as a metabolic waste product and cause of muscle fatigue, a contemporary view incorporates the roles of lactate in metabolism, sensing and signaling in normal as well as pathophysiological conditions. Lactate exists in millimolar concentrations in muscle, blood and other tissues and can rise more than an order of magnitude as the result of increased production and clearance limitations. Lactate exerts its powerful driver-like influence by mass action, redox change, allosteric binding, and other mechanisms described in this article. Depending on the condition, such as during rest and exercise, following injury, or pathology, lactate can serve as a myokine or exerkine with autocrine-, paracrine-, and endocrine-like functions that have important basic and translational implications. For instance, lactate signaling is: involved in reproductive biology, fueling the heart, muscle and brain, controlling cardiac output and breathing, growth and development, and a treatment for inflammatory conditions. Ironically, lactate can be disruptive of normal processes such as insulin secretion when insertion of lactate transporters into pancreatic Beta-cell membranes is not suppressed and in carcinogenesis. Lactate signaling is important in areas of intermediary metabolism, redox biology, mitochondrial biogenesis, cardiovascular and pulmonary regulation, genomics, neurobiology, gut physiology, appetite regulation, nutrition and overall health and vigor. The various roles of lactate as a myokine and exerkine are reviewed.
... The inconsistency associated with the reduced desacylated ghrelin concentrations post-exercise observed in other previous studies could be attributed to the difference in the exercise duration i.e., 30 minutes vs. 60 minutes) since exercise duration has been known to influence ghrelin response [36]; however, this needs more corroborating evidence. Much of the literature has revealed the following observations during or after acute exercise: blood distribution [36], up-and-down motion of the center of the body [37] and lactate accumulation [38]. This may explain the reduction in acylated ghrelin concentration during this period. ...
... In contrast to previous studies [38,44,45], the transient suppression of subjective hunger after exercise, often termed exercise-induced anorexia [9], was not observed in the present study, although a suppressive effect was noted after meal consumption. Thus, it is difficult to address, at least in our study, whether exercise-induced anorexia, typically seen after high-intensity exercise, may be potentially linked to the decreased acylated ghrelin levels observed immediately after exercise. ...
Ample evidence supports the notion that an acute bout of aerobic exercise and meal consumption reduces acylated ghrelin concentration. However, the mechanisms by which this exercise- and meal-induced suppression of acylated ghrelin occurs in humans is unknown. This study aimed to examine the concentration of butyrylcholinesterase (BChE), an enzyme responsible for hydrolysing ghrelin and other appetite-related hormones in response to a single bout of running and a standardised meal in young, healthy men. Thirty-three men (aged 23 ± 2 years, mean ± standard deviation) underwent two (exercise and meal conditions) 2-h laboratory-based experiments. In the exercise condition, all participants ran for 30 min at 70% of the maximum oxygen uptake (0930–1000) and rested until 1130. In the meal condition, participants reported to the laboratory at 0930 and rested until 1000. Subsequently, they consumed a standardised meal (1000–1015) and rested until 1130. Blood samples were collected at baseline (0930), 1000, 1030, 1100 and 1130. BChE concentration was not altered in both the exercise and meal conditions (p > 0.05). However, acylated ghrelin was suppressed after exercise (p < 0.05) and meal consumption (p < 0.05). There was no association between the change in BChE concentration and the change in acylated ghrelin before and after exercise (p = 0.571). Although des-acylated ghrelin concentration did not change during exercise (p > 0.05), it decreased after meal consumption (p < 0.05). These findings suggest that BChE may not be involved in the suppression of acylated ghrelin after exercise and meal consumption.
... Additionally, the meta-analysis undertaken by Atakan et al. in 2022 [48] found that interval training boosted fat oxidation (0.04-0.12 g/min) at a rate higher than MICT (0.01-0.05 g/min) during exercise, especially in overweight individuals. Low-volume interval training also increases the concentration of blood lactate which could suppress appetite (affects ghrelin, peptide YY, and glucagon-like peptide-1), and consequently reduces energy intake [52] . It should be noted that the above is only a preliminary explanation of the fat loss mechanism of low-volume interval training, and some of them are still controversial, such as whether the duration and total volume of EPOC of low-volume interval training are su cient to achieve fat loss, whether the transient suppression of appetite by low-volume interval training leads to long-term reduction of dietary intake, and whether the enhancement of lipolytic capacity and oxidative rate induced by long-term low-volume interval training could result in a meaningful fat loss. ...
Background
Interval training can be classified into high-intensity interval training (HIIT, 80%-100%V̇O2max) and sprint interval training (SIT, ≥ 100%V̇O2max) according to exercise intensity. HIIT can be further divided into high-volume HIIT (HV-HIIT, pure training time ≥ 15min/session) and low-volume HIIT (LV-HIIT, pure training time < 15min/session). The effectiveness of HV-HIIT in reducing body fat among adults has been well-proven, but there is a lack of comprehensive analysis on the impacts of low-volume interval training (i.e. LV-HIIT and SIT) on fat loss.
Objective
The systematic review and meta-analysis aim to determine the effectiveness of low-volume interval training in improving whole-body fat, abdominal and visceral fat in adults living with overweight and obesity.
Methods
Following the PRISMA guidelines and inclusion criteria, eligible articles were extracted from seven electronic databases and the reference lists of key papers in the field. The search was limited to English articles published on and before May 2023. Effect sizes were calculated as standardized mean difference (SMD) for four intervention outcomes, whole-body fat, body fat percentage, abdominal fat, and visceral fat.
Results
Out of the 4568 identified studies, a total of 50 randomized controlled trials were included, involving 1843 participants (age: 19.8 to 70.5 years, BMI: 25 to 39.5 kg/m²). The low-volume interval training protocol included in this review had an average training duration of 9.5 weeks, a frequency of 3.3 times per week, an exercise session time of 6.2 minutes, and an exercise intensity of ≥ 80%V̇O2max or HRmax. Compared to the comparator groups of no-exercising (CON), low-volume interval training significantly reduced whole-body fat mass (-6.4%, p < 0.001), body fat percentage (-5.3%, p < 0.001), abdominal fat (-5.8%, p = 0.02) and visceral fat (-12.6%, p < 0.001). Compared to moderate-intensity continuous training (MICT), low-volume interval training showed a significant reduction in visceral fat (-3.9%, p = 0.04). No significant differences were observed between low-volume interval training and HV-HIIT in four outcome measures.
Conclusion
Low-volume interval training (LV-HIIT and SIT) groups show significant reductions in whole-body, abdominal and visceral fat among overweight and obese adults. It is more effective than MICT in reducing visceral fat. These findings emphasize the efficiency of low-volume interval training as an intervention for fat loss.
The study protocol was registered (Registration No.: CRD42022341699) with the International Prospective Register of Systematic Reviews (PROSPERO).
... With regard to the "all-out" nature of SIT, potentially greater muscle glycogen depletion, post-exercise oxygen consumption (Moniz et al., 2020), and higher rates of hormonedriven lipolysis (Pritzlaff et al., 2000;Trapp et al., 2007) might account for the similar outcomes on fat reduction between SIT and MICT or HIIT with a lower intensity. Possibly, SIT might have induced a decreased post-exercise appetite via lactate accumulation (Vanderheyden et al., 2020), and thus daily energy intake in SIT was less than MICT and CON (i.e., ~200-300 kcal less) despite no significant differences. Nonetheless, short-term SIT interventions (i.e., 2-5 weeks) failed to elicit significant changes in body composition in the literature (Kong et al., 2016;Skleryk et al., 2013), suggesting that a long adhering period to SIT (i.e., ≥ 12 weeks) may be a determining factor to produce meaningful fat reductions in overweight populations. ...
This study examined the effects of 12 weeks of sprint interval training (SIT), high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cardiorespiratory fitness (peak oxygen uptake, VO 2peak), body composition and physical activity enjoyment in overweight young women. Sixty-six participants (age 21.2 ± 1.4 years, body mass index (BMI) 26.0 ± 3.0 kg·m −2 , body fat percentage 39.0 ± 2.8%) were randomly assigned to non-exercise control (CON), thrice-weekly SIT (80 × 6 s "all-out" cycling interspersed with 9 s rest), and HIIT (4 min cycling at 90% VO 2peak followed with 3 min recovery for ~ 60 min) or MICT (~ 65 min continuous cycling at 60% VO 2peak) with equivalent mechanical work (200/ 300 KJ). Compared to the CON group, all three training groups had significant and similar improvements in VO 2peak (~ +20%, d = 2.5-3.4), fat mass (~ −10%, d = 1.3-2.1) and body fat percentage (~ −5%, d = 1.0-1.1) after a 12-week intervention. Similar high levels of enjoyment were observed among groups for most (~70%) of the training sessions. The findings suggest that the three training regimes are equally enjoyable and could result in similar improvements in cardiorespiratory fitness and body composition in overweight/obese young women, but SIT is a more time-efficient strategy. ARTICLE HISTORY
... For instance, few are hungry immediately after maximal exercise to exhaustion. The suppressive effect of lactate on appetite (Schmid et al. 2008;Schultes et al. 2012;McCarthy et al. 2020) is consistent with data showing that lactataemia suppresses ghrelin secretion (Islam et al. 2017;Vanderheyden et al. 2020). The ghrelin receptor (growth hormone secretagogue receptor (GHSR-1α)) is a G-protein coupled receptor expressed throughout both the stomach and GI tract. ...
After a Century, it's time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling is an important component of intermediary metabolism in vivo. Cell‐Cell and intracellular Lactate Shuttles fulfill purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where the roles of driver (producer) and recipient (consumer) cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal and satiety signaling has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristic such as improved physical work capacity, metabolic flexibility, learning, and memory. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signaling and shuttling are dysregulated as occur in particular illnesses and injuries. Like a Phoenix, lactate has risen to major importance in 21st Century Biology. This article is protected by copyright. All rights reserved
... Moreover, it has been reported that exercise intensity may differentially affect physiological mechanisms involved in appetite regulation. While low-and moderate-intensity exercise appear to have little impact on appetite perception 73 , it has been demonstrated that high-intensity exercise may have appetite-suppressing effects, which were associated with exercise-induced changes in peripheral gut hormones like ghrelin 74 and modifications in brain receptors controlling central appetite regulation 75 www.nature.com/scientificreports/ to the MIIT group supports these previous findings. However, there is still lack of evidence whether HIIT actually leads to lower energy intake over the longer term when compared to moderate-intensity exercise 76 . ...
Physical activity is a cornerstone in the treatment of obesity and metabolic syndrome (MetS). Given the leading physical activity barrier of time commitment and safety concerns about vigorous exercise in high-risk groups, this study aimed to investigate the effects of two extremely time-efficient training protocols (< 30 min time effort per week), either performed as high- (HIIT) or moderate-intensity interval training (MIIT) over 12 weeks, in obese MetS patients. In total, 117 patients (49.8 ± 13.6 years, BMI: 38.2 ± 6.2 kg/m ² ) were randomized to HIIT (n = 40), MIIT (n = 37) or an inactive control group (n = 40). All groups received nutritional counseling to support weight loss. Maximal oxygen uptake (VO 2max ), MetS severity (MetS z-score), body composition and quality of life (QoL) were assessed pre-and post-intervention. All groups significantly reduced body weight (~ 3%) but only the exercise groups improved VO 2max , MetS z-score and QoL. VO 2max (HIIT: + 3.1 mL/kg/min, p < 0.001; MIIT: + 1.2 mL/kg/min, p < 0.05) and MetS z-score (HIIT: − 1.8 units, p < 0.001; MIIT: − 1.2 units, p < 0.01) improved in an exercise intensity-dependent manner. In conclusion, extremely low-volume interval training, even when done at moderate intensity, is sufficiently effective to improve cardiometabolic health in obese MetS patients. These findings underpin the crucial role of exercise in the treatment of obesity and MetS.
... For instance, few are hungry immediately after maximal exercise to exhaustion. The suppressive effect of lactate on appetite (Schmid et al. 2008;Schultes et al. 2012;McCarthy et al. 2020) is consistent with data showing that lactataemia suppresses ghrelin secretion (Islam et al. 2017;Vanderheyden et al. 2020). The ghrelin receptor (growth hormone secretagogue receptor (GHSR-1α)) is a G-protein coupled receptor expressed throughout both the stomach and GI tract. ...
After a Century it is time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling as an important component of intermediary metabolism in vivo. Cell-Cell and intracellular Lactate Shuttles fulfill purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where roles of driver and recipient cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristic such as improved physical work capacity, metabolic flexibility and cognition. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signaling and shuttling are dysregulated as occur in illness and injury. Like a Phoenix, lactate rises again in importance in 21st Century Biology.
... Fortunately, however, there is growing data on the suppressive effect of lactate on appetite [61,62]. In this regard recent results of Hazell and colleagues in studying endocrine responses to hard exercise support the hypothesis that lactatemia results in appetite suppression via ghrelin secretion [63,64], ghrelin released from the stomach upon the appearance of food being one of the major stimulators of appetite via action on the arcuate nucleus in the hypothalamus. ...
As exercise intensity exceeds 65% of maximal oxygen uptake carbohydrate energy sources predominate. However, relative to the meager 4–5 g blood glucose pool size in a postabsorptive individual (0.9–1.0 g·L−1 × 5 L blood = 18–20 kcal), carbohydrate (CHO) oxidation rates of 20 kcal·min−1 can be sustained in a healthy and fit person for one hour, if not longer, all the while euglycemia is maintained. While glucose rate of appearance (i.e., production, Ra) from splanchnic sources in a postabsorptive person can rise 2–3 fold during exercise, working muscle and adipose tissue glucose uptake must be restricted while other energy substrates such as glycogen, lactate, and fatty acids are mobilized and utilized. If not for the use of alternative energy substrates hypoglycemia would occur in less than a minute during hard exercise because blood glucose disposal rate (Rd) could easily exceed glucose production (Ra) from hepatic glycogenolysis and gluconeogenesis. The goal of this paper is to present and discuss the integration of physiological, neuroendocrine, circulatory, and biochemical mechanisms necessary for maintenance of euglycemia during sustained hard physical exercise.
An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight‐loss treatment. Metabolic responses to acute exercise are, however, dependent on pre‐exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise‐induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon‐like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, −48.8 pmol/L; exercise: −22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma ¹ H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise‐induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. image
Key points
Carbohydrate and exercise independently influence key appetite‐regulating hormones.
Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY.
Postexercise energy intake is associated with glucagon‐like peptide 1 and succinate levels.
Obesity is one of the major pandemics of the 21st century. Due to its multifactorial etiology, its treatment requires several actions, including dietary intervention and physical exercise. Excessive fat accumulation leads to several health problems involving alteration in the gut-microbiota-brain axis. This axis is characterized by multiple biological systems generating a network that allows bidirectional communication between intestinal bacteria and brain. This mutual communication maintains the homeostasis of the gastrointestinal, central nervous and microbial systems of animals. Moreover, this axis involves inflammatory, neural, and endocrine mechanisms, contributes to obesity pathogenesis. The axis also acts in appetite and satiety control and synthesizing hormones that participate in gastrointestinal functions. Exercise is a nonpharmacologic agent commonly used to prevent and treat obesity and other chronic degenerative diseases. Besides increasing energy expenditure, exercise induces the synthesis and liberation of several muscle-derived myokines and neuroendocrine peptides such as neuropeptide Y, peptide YY, ghrelin, and leptin, which act directly on the gut-microbiota-brain axis. Thus, exercise may serve as a rebalancing agent of the gut-microbiota-brain axis under the stimulus of chronic low-grade inflammation induced by obesity. So far, there is little evidence of modification of the gut-brain axis as a whole, and this narrative review aims to address the molecular pathways through which exercise may act in the context of disorders of the gut-brain axis due to obesity.
High-intensity intermittent exercise (HIIE) has been shown to transiently suppress appetite, but such exercise has traditionally required the use of specialist apparatus (e.g., cycle ergometer). This study aimed to determine appetite and eating behaviour responses to acute apparatus-free HIIE in inactive women with excess weight. A preliminary study (n=18 inactive women, 9 healthy weight, 18.0-24.9kg∙m⁻²; 9 with excess weight, 25.0-34.9kg∙m⁻²) revealed that intervals of 30 seconds of “all out” star jumping elicited physiological responses akin to intervals of 30 seconds of “all out” cycling. Twelve women (29.2±2.9kg∙m⁻², 38±7years, 28±39minutes MVPA∙week⁻¹) then completed three trials in a within-subject, randomised cross-over design: 4 × 30sec “all out” star jumping (4 × 30sec); 2 × 30sec “all out” star jumping (2 × 30sec); resting control (CONT). Upon completing each late-morning exercise trial, lunch was provided upon request from the participant. The time from the exercise bout to lunch request – termed eating latency – was recorded, and ad libitum food intake at lunch was measured. Subjective appetite was measured using a visual analogue scale before and after exercise, and at lunch request. Free-living energy intake (EI) and energy expenditure (EE) were recorded for the remainder of the trial day and the three days following. Change-from-baseline in subjective appetite was significantly lower immediately after 4 × 30sec (-9.6±18.4mm) and 2 × 30sec (-11.5±21.2mm) vs. CONT (+8.1±9.6mm), (both p < 0.05, d = 0.905 and 1.027, respectively). Eating latency (4 × 30sec: 32±33min, 2 × 30sec: 31±26min, CONT: 27±23min, p = 0.843; η²p = 0.017) and lunch EI (4 × 30sec: 662±178kcal, 2 × 30sec: 715±237kcal, CONT: 726±268kcal, p = 0.451; η²p = 0.077) did not differ significantly between conditions. No significant differences were observed in trial day EI and EE, or in EI and EE on the three days following exercise (all p > 0.05). Mean trial day relative EI (EI – EE) was 201±370kcal lower after 4 × 30sec than CONT, but this difference was not statistically significant (p = 0.303, d = 0.585). In conclusion, very low-volume star jumping elicited a transient suppression of appetite without altering eating behaviour. (313 words)
Lactate, a molecule originally considered metabolic waste, is now associated with a number of important physiological functions. Although the roles of lactate as a signaling molecule, fuel source, and gluconeogenic substrate have garnered significantly attention in recent reviews, a relatively underexplored and emerging role of lactate is its control of energy intake (EI). To expand our understanding of the physiological roles of lactate, we present evidence from early infusion studies demonstrating the ability of lactate to suppress EI in both rodents and humans. We then discuss findings from recent human studies that have utilized exercise intensity and/or sodium bicarbonate supplementation to modulate endogenous lactate and examine its impact on appetite regulation. These studies consistently demonstrate that greater blood lactate accumulation is associated with greater suppression of the hunger hormone ghrelin and subjective appetite, thereby supporting a role of lactate in the control of EI. To stimulate future research investigating the role of lactate as an appetite-regulatory molecule, we also highlight potential underlying mechanisms explaining the appetite suppressive effects of lactate using evidence from rodent and in vitro cellular models. Specifically, we discuss the ability of lactate to: 1) inhibit the secretory function of ghrelin producing gastric cells, 2) modulate the signaling cascades that control hypothalamic neuropeptide expression/release, and 3) inhibit signaling through the ghrelin receptor in the hypothalamus. Unravelling the role of lactate as an appetite-regulatory molecule can shed important insight into the regulation of EI, thereby contributing to the development of interventions aimed at combatting overweight and obesity.
Background:
There is individual responsiveness to exercise training as not all individuals experience increases in maximal oxygen uptake (VO2max), which does not benefit health status considering the association between VO2max and mortality. Approximately 50% of the training response is genetic, with the other 50% accounted for by variations in dietary intake, sleep, recovery, and the metabolic stress of training. This study examined if the blood lactate (BLa) response to high intensity interval training (HIIT) as well as habitual dietary intake and sleep duration are associated with the resultant change in VO2max (ΔVO2max).
Methods:
Fourteen individuals (age and VO2max = 27 ± 8 years and 38 ± 4 mL/kg/min, respectively) performed nine sessions of HIIT at 130% ventilatory threshold. BLa was measured during the first and last session of training. In addition, sleep duration and energy intake were assessed.
Results:
Data showed that VO2max increased with HIIT (p = 0.007). No associations occurred between ΔVO2max and BLa (r = 0.44, p = 0.10), energy intake (r = 0.38, p = 0.18), or sleep duration (r = 0.14, p = 0.62). However, there was a significant association between training heart rate (HR) and ΔVO2max (r = 0.62, p = 0.02).
Conclusions:
When HIIT is prescribed according to a metabolic threshold, energy intake, sleep status, and BLa do not predict ΔVO2max, yet the HR response to training is associated with the ΔVO2max.
Purpose:
Long-term effects of exercise training are well studied. Acute hemodynamic responses to various training modalities, in particularly strength training (ST), have only been described in a few studies. This study examines the acute responses to ST, high-intensity interval training (HIIT) and moderate-intensity continuous training (MCT).
Methods:
Twelve young male subjects (age 23.4 ± 2.6 years; BMI 23.7 ± 1.5 kg/m²) performed an incremental exertion test and were randomized into HIIT (4 × 4-min intervals), MCT (continuous cycling) and ST (five body-weight exercises) which were matched for training duration. The cardiopulmonary (impedance cardiography, ergo-spirometry) and metabolic response were monitored.
Results:
Similar peak blood lactate responses were observed after HIIT and ST (8.5 ± 2.6 and 8.1 ± 1.2 mmol/l, respectively; p = 0.83). The training impact time was 90.7 ± 8.5% for HIIT and 68.2 ± 8.5% for MCT (p < 0.0001). The mean cardiac output was significantly higher for HIIT compared to that of MCT and ST (23.2 ± 4.1 vs. 20.9 ± 2.9 vs. 12.9 ± 2.9 l/min, respectively; p < 0.0001). VO2max was twofold higher during HIIT compared to that observed during ST (2529 ± 310 vs. 1290 ± 156 ml; p = 0.0004). Among the components of ST, squats compared with push-ups resulted in different heart rate (111 ± 13.5 vs. 125 ± 15.7 bpm, respectively; p < 0.05) and stroke volume (125 ± 23.3 vs. 104 ± 19.8 ml, respectively; p < 0.05).
Conclusions:
Despite an equal training duration and a similar acute metabolic response, large differences with regard to the training impact time and the cardiopulmonary response give evident. HIIT and MCT, but less ST, induced a sufficient cardiopulmonary response, which is important for the preventive effects of training; however, large differences in intensity were apparent for ST.
IL-6 is secreted from muscles to the circulation during high-intensity and long-duration exercise, where muscle-derived IL-6 works as an energy sensor to increase release of energy substrates from liver and adipose tissues. We investigated the mechanism involved in the exercise-mediated surge in IL-6 during exercise. Using interval-based cycling in healthy young men, swimming exercise in mice, and electrical stimulation of primary human muscle cells, we explored the role of lactate production in muscular IL-6 release during exercise. First, we observed a tight correlation between lactate production and IL-6 release during both strenuous bicycling and electrically stimulated muscle cell cultures. In mice, intramuscular injection of lactate mimicked the exercise-dependent release of IL-6, and pH buffering of lactate production during exercise attenuated IL-6 secretion. Next, we used in vivo bioimaging to demonstrate that intrinsic intramuscular proteases were activated in mice during swimming, and that blockade of protease activity blunted swimming-induced IL-6 release in mice. Last, intramuscular injection of the protease hyaluronidase resulted in dramatic increases in serum IL-6 in mice, and immunohistochemical analyses showed that intramuscular lactate and hyaluronidase injections led to release of IL-6-containing intramyocellular vesicles. We identified a pool of IL-6 located within vesicles of skeletal muscle fibers, which could be readily secreted upon protease activity. This protease-dependent release of IL-6 was initiated by lactate production, linking training intensity and lactate production to IL-6 release during strenuous exercise.
Once thought to be a waste product of anaerobic metabolism, lactate is now known to form continuously under aerobic conditions. Shuttling between producer and consumer cells fulfills at least three purposes for lactate: (1) a major energy source, (2) the major gluconeogenic precursor, and (3) a signaling molecule. "Lactate shuttle" (LS) concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signaling. In medicine, it has long been recognized that the elevation of blood lactate correlates with illness or injury severity. However, with lactate shuttle theory in mind, some clinicians are now appreciating lactatemia as a "strain" and not a "stress" biomarker. In fact, clinical studies are utilizing lactate to treat pro-inflammatory conditions and to deliver optimal fuel for working muscles in sports medicine. The above, as well as historic and recent studies of lactate metabolism and shuttling, are discussed in the following review.
High-intensity exercise suppresses appetite partly through changes in peripheral appetite-regulating hormones. Lactate and interleukin-6 (IL-6) mediate the release of these hormones in animal/cell models and may provide a mechanistic link between exercise intensity and appetite regulation. The current study examined changes in appetite-regulating hormones, lactate, and IL-6 after different intensities of running. Eight males completed four experimental sessions: 1) Moderate-intensity continuous training (MICT; 65% VO2max); 2) Vigorous-intensity continuous training (VICT; 85% VO2max); 3) Sprint interval training (SIT; repeated "all-out" sprints); 4) Control (CTRL; no exercise). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), total peptide YY (PYY), lactate, IL-6, and appetite perceptions were measured pre-, immediately post-, 30 min post-, and 90 min post-exercise. Energy intake was recorded over 3 days. VICT and SIT suppressed ghrelin (p<0.001), though SIT elicited a greater (p=0.016 vs. MICT) and more prolonged (p<0.001 vs. all sessions) response. GLP-1 increased immediately after MICT (p<0.001) and 30 min after VICT (p<0.001) and SIT (p<0.002), while VICT elicited a greater post-exercise increase in PYY versus MICT (p=0.027). Post-exercise changes in blood lactate and IL-6 correlated with the area under the curve values for ghrelin (r=-0.60, p<0.001) and GLP-1 (r=0.42, p=0.017), respectively. Appetite was suppressed after exercise (p<0.001), though more so after VICT (p<0.027) and SIT (p<0.001) versus MICT and energy intake was reduced on the day after VICT (p<0.017 versus MICT and CTRL) and SIT (p=0.049 versus MICT). These findings support an intensity-dependent paradigm for appetite regulation following exercise and highlight the potential involvement of lactate and IL-6.
This study aimed to examine the blood lactate and blood pH kinetics during high-intensity interval training. Seventeen well-trained athletes exercised on two different occasions. Exercises consisted of three 30 s bouts at a constant intensity (90% of peak power) with 4 min recovery between bouts followed by a Wingate test (WT). The recoveries were either active recovery (at 60% of the lactate threshold intensity) or passive recovery (resting at sitting position). During the exercise, blood samples were taken to determine blood gasses, blood lactate, and blood pH, and peak and average power were calculated for the WT. When performing the active recovery trials, blood pH was significantly higher (p < 0.01) and blood lactate was significantly lower (p < 0.01) compared with the passive recovery trials. WT performance was significantly higher in the active recovery trials: peak power was 671 ± 88 and 715 ± 108 watts, and average power was 510 ± 70 and 548 ± 73 watts (passive and active respectively; p < 0.01). However, no statistically significant correlations were found between the increased pH and the increased performance in the active recovery trials. These results suggest that active recovery performed during high-intensity interval exercise favors the performance in a following WT. Moreover, the blood pH variations associated with active recovery did not explain the enhanced performance.
We compared the acute response of anorexigenic signals (total PYY and GLP-1) in response to submaximal and supramaximal exercise. Nine females completed three sessions: (1) moderate-intensity continuous training (MICT; 30 min; 65% VO2max ); (2) sprint interval training (SIT; 6 × 30 sec “all-out” cycling sprints with 4 min recovery); or (3) control (CTRL; no exercise). PYY and GLP-1 were measured via blood samples drawn before, immediately after, and 90 min after exercise. Perceptions of hunger were rated using a visual analogue scale at all blood sampling time points. There was a session × time interaction for GLP-1 ( p=0.004 ) where SIT and MICT ( p<0.015 and p<0.001 ) were higher compared to CTRL both immediately and 90 min after exercise. There was a main effect of time for PYY where 90 min after exercise it was decreased versus before and immediately after exercise. There was a session × time interaction for hunger with lower ratings following SIT versus MICT ( p=0.027 ) and CTRL ( p=0.031 ) 90 min after exercise. These results suggest that though GLP-1 is elevated after exercise in women, it is not affected by exercise intensity though hunger was lower 90 min after exercise with SIT. As the sample size is small further study is needed to confirm these findings.
The maximum rate of VO2 uptake (i.e., VO2max), as measured during large muscle mass exercise such as cycling or running, is widely considered to be the gold standard measurement of integrated cardiopulmonary-muscle oxidative function. The development of rapid-response gas analyzers, enabling measurement of breath-by-breath pulmonary gas exchange, has led to replacement of the discontinuous progressive maximal exercise test (that produced an unambiguous VO2-work rate plateau definitive for VO2max) with the rapidly-incremented or ramp testing protocol. Whilst this expedient is more suitable for clinical and experimental investigations and enables measurement of the gas exchange threshold, exercise efficiency, and VO2 kinetics, a VO2-work rate plateau is not an obligatory outcome. This shortcoming has led to investigators resorting to so-called secondary criteria such as respiratory exchange ratio, maximal heart rate and/or maximal blood lactate concentration, the acceptable values of which may be selected arbitrarily and result in grossly inaccurate VO2max determination. Whereas this may not be an overriding concern in young, healthy subjects with experience of performing exercise to volitional exhaustion, exercise test naïve subjects, patient populations and less motivated subjects may stop exercising before their VO2max is reached. When VO2max is a or the criterion outcome of the investigation this represents a major experimental design issue. This CORP presents the rationale for incorporation of a second, constant-work rate test performed at 105-110% of the work rate achieved on the initial ramp test to resolve the classic VO2-work rate plateau that is the unambiguous validation of VO2max. The broad utility of this procedure has been established for children, adults of varying fitness, obese individuals and patient populations.
A large proportion of empirical research and reviews investigating the ergogenic potential of sodium bicarbonate (NaHCO3) supplementation have focused predominately on performance outcomes and only speculate about underlying mechanisms responsible for any benefit. The aim of this review was to critically evaluate the influence of NaHCO3 supplementation on mechanisms associated with skeletal muscle fatigue as it translates directly to exercise performance. Mechanistic links between skeletal muscle fatigue, proton accumulation (or metabolic acidosis) and NaHCO3 supplementation have been identified to provide a more targeted, evidence-based approach to direct future research, as well as provide practitioners with a contemporary perspective on the potential applications and limitations of this supplement. The mechanisms identified have been broadly categorised under the sections ‘Whole-body Metabolism’, ‘Muscle Physiology’ and ‘Motor Pathways’, and when possible, the performance outcomes of these studies contextualized within an integrative framework of whole-body exercise where other factors such as task demand (e.g. large vs. small muscle groups), cardio-pulmonary and neural control mechanisms may outweigh any localised influence of NaHCO3. Finally, the ‘Performance Applications’ section provides further interpretation for the practitioner founded on the mechanistic evidence provided in this review and other relevant, applied NaHCO3 performance-related studies.
Lactate (or its protonated form: lactic acid) has been studied by many exercise scientists. The lactate paradigm has been in constant change since lactate was first discovered in 1780. For many years, it was unfairly seen as primarily responsible for muscular fatigue during exercise and a waste product of glycolysis. The status of lactate has slowly changed to an energy source, and in the last two decades new evidence suggests that lactate may play a much bigger role than was previously believed: many adaptations to exercise may be mediated in some way by lactate. The mechanisms behind these adaptations are yet to be understood. The aim of this review is to present the state of lactate science, focusing on how this molecule may mediate exercise-induced adaptations.
We tested the hypothesis that ingestion of sodium bicarbonate (NaHCO3) prior to an acute session of high-intensity interval training (HIIT) would augment signalling cascades and gene expression linked to mitochondrial biogenesis in human skeletal muscle. On two occasions separated by ~1 wk, nine men (22±2 y; 78±13 kg, VO2peak = 48±8 mL kg(-1) min(-1); mean ± SD) performed 10x60-s cycling efforts at an intensity eliciting ~90% of maximal heart rate (263±40 W), interspersed with 60 s of recovery. In a double-blind, crossover manner, subjects ingested a total of 0.4 g kg b.w.(-1) NaHCO3 prior to exercise (BICARB) or an equimolar amount of the placebo, sodium chloride (PLAC). Venous blood bicarbonate and pH were elevated at all time points post-ingestion (p<0.05) in BICARB vs. PLAC. During exercise, muscle glycogen utilization (126±47 vs. 53±38 mmol kg d.w.(-1); p < 0.05) and blood lactate accumulation (12.8±2.6 vs. 10.5±2.8 mmol L(-1); p < 0.05) were greater in BICARB vs. PLAC. The acute exercise-induced increase in the phosphorylation of acetyl-CoA carboxylase, a downstream marker of AMP-activated protein kinase activity, and p38 mitogen-activated protein kinase were similar between treatments (p>0.05). However, the increase in PGC-1α mRNA expression after 3 h of recovery was higher in BICARB vs. PLAC (~7- vs. 5-fold compared to rest, p<0.05). We conclude that NaHCO3 prior to HIIT alters the mRNA expression of this key regulatory protein associated with mitochondrial biogenesis. The elevated PGC-1α mRNA response provides a putative mechanism to explain the enhanced mitochondrial adaptation seen after chronic NaHCO3-supplemented HIIT in rats.
Purpose
We have previously shown that 6 weeks of reduced-exertion high-intensity interval training (REHIT) improves V˙O2max in sedentary men and women and insulin sensitivity in men. Here, we present two studies examining the acute physiological and molecular responses to REHIT.
Methods
In Study 1, five men and six women (age: 26 ± 7 year, BMI: 23 ± 3 kg m−2, V˙O2max: 51 ± 11 ml kg−1 min−1) performed a single 10-min REHIT cycling session (60 W and two 20-s ‘all-out’ sprints), with vastus lateralis biopsies taken before and 0, 30, and 180 min post-exercise for analysis of glycogen content, phosphorylation of AMPK, p38 MAPK and ACC, and gene expression of PGC1α and GLUT4. In Study 2, eight men (21 ± 2 year; 25 ± 4 kg·m−2; 39 ± 10 ml kg−1 min−1) performed three trials (REHIT, 30-min cycling at 50 % of V˙O2max, and a resting control condition) in a randomised cross-over design. Expired air, venous blood samples, and subjective measures of appetite and fatigue were collected before and 0, 15, 30, and 90 min post-exercise.
Results
Acutely, REHIT was associated with a decrease in muscle glycogen, increased ACC phosphorylation, and activation of PGC1α. When compared to aerobic exercise, changes in V˙O2, RER, plasma volume, and plasma lactate and ghrelin were significantly more pronounced with REHIT, whereas plasma glucose, NEFAs, PYY, and measures of appetite were unaffected.
Conclusions
Collectively, these data demonstrate that REHIT is associated with a pronounced disturbance of physiological homeostasis and associated activation of signalling pathways, which together may help explain previously observed adaptations once considered exclusive to aerobic exercise.
A cumulative effect of reduced energy intake, increased oxygen consumption, and/or increased lipid oxidation could explain the fat loss associated with sprint interval exercise training (SIT). This study assessed the effects of acute sprint interval exercise (SIE) on energy intake, subjective appetite, appetite-related peptides, oxygen consumption, and respiratory exchange ratio over 2 days. Eight men (25 ± 3 years, 79.6 ± 9.7 kg, body fat 13% ± 6%; mean ± SD) completed 2 experimental treatments: SIE and recovery (SIEx) and nonexercise control. Each 34-h treatment consisted of 2 consecutive 10-h test days. Between 0800-1800 h, participants remained in the laboratory for 8 breath-by-breath gas collections, 3 buffet-type meals, 14 appetite ratings, and 4 blood samples for appetite-related peptides. Treatment comparisons were made using 2-way repeated measures ANOVA or t tests. An immediate, albeit short-lived (<1 h), postexercise suppression of appetite and increase in peptide YY (PYY) were observed (P < 0.001). However, overall hunger and motivation to eat were greater during SIEx (P < 0.02) without affecting energy intake. Total 34-h oxygen consumption was greater during SIEx (P = 0.04), elicited by the 1491-kJ (22%) greater energy expenditure over the first 24 h (P = 0.01). Despite its effects on oxygen consumption, appetite, and PYY, acute SIE did not affect energy intake. Consequently, if these dietary responses to SIE are sustained with regular SIT, augmentations in oxygen consumption and/or a substrate shift toward increased fat use postexercise are most likely responsible for the observed body fat loss with this type of exercise training.
Energy intake (EI) and physical activity energy expenditure (PAEE) are key modifiable determinants of energy balance, traditionally assessed by self-report despite its repeated demonstration of considerable inaccuracies. We argue here that it is time to move from the common view that self-reports of EI and PAEE are imperfect, but nevertheless deserving of use, to a view commensurate with the evidence that self-reports of EI and PAEE are so poor that they are wholly unacceptable for scientific research on EI and PAEE. While new strategies for objectively determining energy balance are in their infancy, it is unacceptable to use decidedly inaccurate instruments, which may misguide health care policies, future research, and clinical judgment. The scientific and medical communities should discontinue reliance on self-reported EI and PAEE. Researchers and sponsors should develop objective measures of energy balance.International Journal of Obesity accepted article preview online, 13 November 2014. doi:10.1038/ijo.2014.199.
The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi/o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi/o pathway: FFAR2 (short chain fatty acid receptor; GPR43), FFAR4 (long chain fatty acid receptor; GPR120) and CasR (calcium sensing receptor). In addition to the common Gα subunits three non-common Gαi/o subunits were highly enriched in ghrelin cells: GαoA, GαoB and Gαz. Inhibition of Gαi/o signaling via ghrelin cell-selective pertussis toxin expression markedly enhanced circulating ghrelin. These 7TM receptors and associated Gα subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the ghrelin cell.
Understanding of the impact of an acute bout of exercise on hormones involved in appetite regulation may provide insight into some of the mechanisms that regulate energy balance. In resting conditions, acylated ghrelin is known to stimulate food intake, while hormones such as peptide YY (PYY), pancreatic polypeptide (PP) and glucagon-like peptide 1 (GLP-1) are known to suppress food intake.
The objective of this review was to determine the magnitude of exercise effects on levels of gastrointestinal hormones related to appetite, using systematic review and meta-analysis. Additionally, factors such as the exercise intensity, duration and mode, in addition to participant characteristics, were examined to determine their influence on these hormones.
Major databases (PubMed, Scopus, Google Scholar, Science Direct, Academic Search Premier and EBSCOHost) were searched, through February 2013, for original studies, abstracts, theses and dissertations that examined responses of appetite hormones to acute exercise.
Studies were included if they evaluated appetite hormone responses during and in the hours after an acute bout of exercise and reported area under the concentration-time curve (AUC) values for more than three datapoints. Studies reporting mean or pre/post-values only were excluded.
Initially, 75 studies were identified. After evaluation of study quality and validity, using the Physiotherapy Evidence Database scale, data from 20 studies (28 trials) involving 241 participants (77.6 % men) had their data extracted for inclusion in the meta-analyses. A random-effects meta-analysis was conducted for acylated ghrelin (n = 18 studies, 25 trials) and PYY (n = 8 studies, 14 trials), with sub-group analyses and meta-regressions being conducted for moderator variables. Because the number of studies was limited, fixed-effects meta-analyses were performed on PP data (n = 4 studies, 5 trials) and GLP-1 data (n = 5 studies, 8 trials).
The results of the meta-analyses indicated that exercise had small to moderate effects on appetite hormone levels, suppressing acylated ghrelin (effect size [ES] Cohen's d value -0.20, 95 % confidence interval [CI] -0.373 to -0.027; median decrease 16.5 %) and increasing PYY (ES 0.24, 95 % CI 0.007 to 0.475; median increase 8.9 %), GLP-1 (ES 0.275, 95 % CI -0.031 to 0.581; median increase 13 %), and PP (ES 0.50, 95 % CI 0.11 to 0.89; median increase 15 %). No significant heterogeneity was detected in any meta-analysis (using Cochrane's Q and I (2)); however, publication biases were detected for all analyses. No moderator variables were observed to moderate the variability among the studies assessing acylated ghrelin and PYY.
The majority of the present literature is acute in nature; therefore, longer-term alterations in appetite hormone concentrations and their influence on food and beverage intake are unknown. Furthermore, our review was limited to English-language studies and studies reporting AUC data.
An acute bout of exercise may influence appetite by suppressing levels of acylated ghrelin while simultaneously increasing levels of PYY, GLP-1 and PP, which may contribute to alterations in food and drink intake after acute exercise. Further longitudinal studies and exploration into mechanisms of action are required in order to determine the precise role these hormones play in long-term appetite responses to an exercise intervention.
High-intensity intermittent exercise induces physiological adaptations similar to energy-matched continuous exercise, but the comparative appetite and energy balance responses are unknown. Twelve healthy males (mean ± SD: age, 22 ± 3 years; body mass index, 23.7 ± 3.0 kg·m(-2); maximum oxygen uptake, 52.4 ± 7.1 mL·kg(-1)·min(-1)) completed three 8 h trials (control, steady-state exercise (SSE), high-intensity intermittent exercise (HIIE)) separated by 1 week. Trials commenced upon completion of a standardized breakfast. Exercise was performed from hour 2 to hour 3. In SSE, 60 min of cycling at 59.5% ± 1.6% of maximum oxygen uptake was performed. In HIIE, ten 4-min cycling intervals were completed at 85.8% ± 4.0% of maximum oxygen uptake, with a 2-min rest between each interval. A standardized lunch and an ad libitum afternoon meal were provided at hours 3.75 and 7, respectively. Appetite ratings and peptide YY3-36 concentrations were measured throughout each trial. Appetite was acutely suppressed during exercise, but more so during HIIE (p < 0.05). Peptide YY3-36 concentrations increased significantly upon cessation of exercise in SSE (p = 0.002), but were highest in the hours after exercise in HIIE (p = 0.05). Exercise energy expenditure was not different between HIIE and SSE (p = 0.649), but perceived exertion was higher in HIIE (p < 0.0005). Ad libitum energy intake did not differ between trials (p = 0.833). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in the SSE and HIIE trials than in the control trial (control, 4759 ± 1268 kJ; SSE, 2362 ± 1224 kJ; HIIE, 2523 ± 1402 kJ; p < 0.0005). An acute bout of energy-matched continuous exercise and HIIE were equally effective at inducing an energy deficit without stimulating compensatory increases in appetite.
Objective:
To examine the acute effects of high-intensity intermittent exercise (HIIE) on energy intake, perceptions of appetite and appetite-related hormones in sedentary, overweight men.
Design:
Seventeen overweight men (body mass index: 27.7±1.6 kg m(-2); body mass: 89.8±10.1 kg; body fat: 30.0±4.3%; VO(2peak): 39.2±4.8 ml kg(-1) min(-1)) completed four 30-min experimental conditions using a randomised counterbalanced design. CON: resting control, MC: continuous moderate-intensity exercise (60% VO(2peak)), HI: high-intensity intermittent exercise (alternating 60 s at 100% VO(2peak) and 240 s at 50% VO(2peak)), VHI: very-high-intensity intermittent exercise (alternating 15 s at 170% VO(2peak) and 60 s at 32% VO(2peak)). Participants consumed a standard caloric meal following exercise/CON and an ad-libitum meal 70 min later. Capillary blood was sampled and perceived appetite assessed at regular time intervals throughout the session. Free-living energy intake and physical activity levels for the experimental day and the day after were also assessed.
Results:
Ad-libitum energy intake was lower after HI and VHI compared with CON (P=0.038 and P=0.004, respectively), and VHI was also lower than MC (P=0.028). Free-living energy intake in the subsequent 38 h remained less after VHI compared with CON and MC (P≤0.050). These observations were associated with lower active ghrelin (P≤0.050), higher blood lactate (P≤0.014) and higher blood glucose (P≤0.020) after VHI compared with all other trials. Despite higher heart rate and ratings of perceived exertion (RPE) during HI and VHI compared with MC (P≤0.004), ratings of physical activity enjoyment were similar between all the exercise trials (P=0.593). No differences were found in perceived appetite between trials.
Conclusions:
High-intensity intermittent exercise suppresses subsequent ad-libitum energy intake in overweight inactive men. This format of exercise was found to be well tolerated in an overweight population.
The precise magnitude of the effect of acute exercise on subsequent energy intake is not well understood. Identifying how large a deficit exercise can produce in energy intake and whether this is compensated for, is important in design of long-term exercise programs for weight loss and weight maintenance. Thus, this paper sought to review and perform a meta-analysis on data from the existing literature. Twenty-nine studies, consisting of 51 trials, were identified for inclusion. Exercise duration ranged from 30 - 120 min at intensities of 36 - 81% VO(2)max, with trials ranging from 2 - 14 hr, and ad libitum test meals offered 0 - 2 hr post-exercise. The outcome variables included absolute energy intake and relative energy intake. A random effects model was employed for analysis due to expected heterogeneity. Results indicated that exercise has a trivial effect on absolute energy intake (n = 51; ES = 0.14, 95% CI: -0.005 to 0.29) and a large effect on relative energy intake (creating an energy deficit, n = 25; ES = - 1.35, 95% CI: -1.64 to -1.05). Despite variability among studies, results suggest that exercise is effective for producing a short-term energy deficit and that individuals tend not to compensate for the energy expended during exercise in the immediate hours after exercise by altering food intake.
Sprint interval exercise improves several health markers but the appetite and energy balance response is unknown. This study compared the effects of sprint interval and endurance exercise on appetite, energy intake and gut hormone responses. Twelve healthy males [mean (SD): age 23 (3) years, body mass index 24.2 (2.9) kg m(-2), maximum oxygen uptake 46.3 (10.2) mL kg(-1) min(-1)] completed three 8 h trials [control (CON), endurance exercise (END), sprint interval exercise (SIE)] separated by 1 week. Trials commenced upon completion of a standardised breakfast. Sixty minutes of cycling at 68.1 (4.3) % of maximum oxygen uptake was performed from 1.75-2.75 h in END. Six 30-s Wingate tests were performed from 2.25-2.75 h in SIE. Appetite ratings, acylated ghrelin and peptide YY (PYY) concentrations were measured throughout each trial. Food intake was monitored from buffet meals at 3.5 and 7 h and an overnight food bag. Appetite (P < 0.0005) and acylated ghrelin (P < 0.002) were suppressed during exercise but more so during SIE. Peptide YY increased during exercise but most consistently during END (P < 0.05). Acylated ghrelin was lowest in the afternoon of SIE (P = 0.018) despite elevated appetite (P = 0.052). Exercise energy expenditure was higher in END than that in SIE (P < 0.0005). Energy intake was not different between trials (P > 0.05). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in END than that in CON (15.7 %; P = 0.006) and SIE (11.5 %; P = 0.082). An acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise.
Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes.
Lactate is increasingly recognised to be more than a simple end product of anaerobic glycolysis. Skeletal muscle and white adipose tissue are considered to be the main sites of lactate production and release. Recent studies have demonstrated that there is a specific G-protein coupled receptor for lactate, GPR81, which is expressed primarily in adipose tissue, and also in muscle. Lactate inhibits lipolysis in adipose tissue by mediating, through GPR81, the anti-lipolytic action of insulin. A high proportion (50 % or more) of the glucose utilised by white adipose tissue is converted to lactate and lactate production by the tissue increases markedly in obesity; this is likely to reflect a switch towards anaerobic metabolism with the development of hypoxia in the tissue. During exercise, there is a shift in fuel utilisation by muscle from lipid to carbohydrate, but this does not appear to be a result of the inhibition of lipolysis in the main adipose tissue depots by muscle-derived lactate. It is suggested instead that a putative autocrine lactate loop in myocytes may regulate fuel utilisation by muscle during exercise, operating via a muscle GPR81 receptor. In addition to being an important substrate, lactate is a key signal in metabolic regulation.
Low-volume high-intensity interval training (HIT) is emerging as a time-efficient exercise strategy for improving health and fitness. This form of exercise has not been tested in type 2 diabetes and thus we examined the effects of low-volume HIT on glucose regulation and skeletal muscle metabolic capacity in patients with type 2 diabetes. Eight patients with type 2 diabetes (63 ± 8 yr, body mass index 32 ± 6 kg/m(2), Hb(A1C) 6.9 ± 0.7%) volunteered to participate in this study. Participants performed six sessions of HIT (10 × 60-s cycling bouts eliciting ∼90% maximal heart rate, interspersed with 60 s rest) over 2 wk. Before training and from ∼48 to 72 h after the last training bout, glucose regulation was assessed using 24-h continuous glucose monitoring under standardized dietary conditions. Markers of skeletal muscle metabolic capacity were measured in biopsy samples (vastus lateralis) before and after (72 h) training. Average 24-h blood glucose concentration was reduced after training (7.6 ± 1.0 vs. 6.6 ± 0.7 mmol/l) as was the sum of the 3-h postprandial areas under the glucose curve for breakfast, lunch, and dinner (both P < 0.05). Training increased muscle mitochondrial capacity as evidenced by higher citrate synthase maximal activity (∼20%) and protein content of Complex II 70 kDa subunit (∼37%), Complex III Core 2 protein (∼51%), and Complex IV subunit IV (∼68%, all P < 0.05). Mitofusin 2 (∼71%) and GLUT4 (∼369%) protein content were also higher after training (both P < 0.05). Our findings indicate that low-volume HIT can rapidly improve glucose control and induce adaptations in skeletal muscle that are linked to improved metabolic health in patients with type 2 diabetes.
Acute energy deficits imposed by food restriction increase appetite and energy intake; however, these outcomes remain unchanged when energy deficits are imposed by exercise.
Our objective was to determine the potential role of acylated ghrelin and peptide YY(3-36) (PYY(3-36)) in mediating appetite and energy intake responses to identical energy deficits imposed by food restriction and exercise.
Twelve healthy males completed three 9-h trials (exercise deficit, food deficit, and control) in a randomized counterbalanced design. Participants ran for 90 min (70% of VO(2) max) at the beginning of the exercise deficit trial and then rested for 7.5 h. Participants remained sedentary throughout the food deficit and control trials. Test meals were consumed by participants at 2 and 4.75 h in all trials. The amount provided in the food deficit trial was restricted so that an energy deficit (equivalent to that imposed by exercise) was induced relative to control. Participants were permitted access to a buffet meal at 8 h.
The energy deficits imposed by food restriction (4820 ± 151 kJ) and exercise (4715 ± 113 kJ) were similar. Appetite and ad libitum energy intake responded in a compensatory fashion to food restriction yet were not influenced by exercise. Plasma acylated ghrelin concentrations increased, whereas PYY(3-36) decreased, in response to food restriction (two-way ANOVA, trial × time interaction, P < 0.001 for each). Exercise did not induce such compensatory responses.
These findings suggest a mediating role of acylated ghrelin and PYY(3-36) in determining divergent feeding responses to energy deficits imposed by food restriction and exercise.
Three portable blood lactate analysers, Lactate Pro (LP), Lactate Scout (LS) and Lactate Plus (L(+)), were evaluated. Analyser reliability and accuracy was assessed. For reliability, intra- and inter-analyser comparisons demonstrated that the LP (intra-TE = 0.5 mM, inter-TE = 0.4 mM) and L(+) (intra-TE = 0.4, inter-TE = 0.4 mM) displayed greater overall reliability than the LS (intra-TE = 1.0, inter-TE = 0.8 mM). At BLa < 4.0 mM, the LP (intra-TE = 0.1 mM) demonstrated greater reliability than the LS (intra-TE = 0.5 mM) and L(+) (intra-TE = 0.4 mM). At BLa > 8.0 mM, the LP (intra-TE = 0.5 mM, inter-TE = 0.4 mM) and L(+) (intra- and inter-TE = 0.4 mM) displayed greater reliability than the LS (intra-TE = 1.1 mM, inter-TE = 0.9 mM). For accuracy, the L(+) (SEE = 0.6 mM) compared more favourably to the LP than the LS (SEE = 1.1 mM). At BLa approximately 1.0-18.0 mM, the LS produced values that were up to 0.9 mM higher than the LP; the L(+) produced BLa that were within +/-0.1 mM. All portable analysers tended to under-read the ABL 700 analyser. The suitability of the LP and L(+) as accurate analysers is supported by strong correlations (r = 0.91 and r = 0.94) and limits of agreement <or=2.1 mM. This study showed that the LP and L(+), compared well to each other, displayed good reliability and accuracy when compared to a laboratory-based analyser. Although the LS also displayed relatively good reliability, it was not as reliable or accurate as the LP or L(+).
1. Skinfold thickness, body circumferences and body density were measured in samples of 308 and ninety-five adult men ranging in age from 18 to 61 years.
2. Using the sample of 308 men, multiple regression equations were calculated to estimate body density using either the quadratic or log form of the sum of skinfolds, in combination with age, waist and forearm circumference.
3. The multiple correlations for the equations exceeded 0.90 with standard errors of approximately ±0.0073 g/ml.
4. The regression equations were cross validated on the second sample of ninety-five men. The correlations between predicted and laboratory-determined body density exceeded 0.90 with standard errors of approximately 0.0077 g/ml.
5. The regression equations were shown to be valid for adult men varying in age and fatness.
The sequence of glucagon-like peptide-1 (7-36) amide (GLP-1) is completely conserved in all mammalian species studied, implying that it plays a critical physiological role. We have shown that GLP-1 and its specific receptors are present in the hypothalamus. No physiological role for central GLP-1 has been established. We report here that intracerebroventricular (ICV) GLP-1 powerfully inhibits feeding in fasted rats. ICV injection of the specific GLP-1-receptor antagonist, exendin (9-39), blocked the inhibitory effect of GLP-1 on food intake. Exendin (9-39) alone had no influence on fast-induced feeding but more than doubled food intake in satiated rats, and augmented the feeding response to the appetite stimulant, neuropeptide Y. Induction of c-fos is a marker of neuronal activation. Following ICV GLP-1 injection, c-fos appeared exclusively in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and this was inhibited by prior administration of exendin (9-39). Both of these regions of the brain are of primary importance in the regulation of feeding. These findings suggest that central GLP-1 is a new physiological mediator of satiety.
To examine reproducibility and validity of visual analogue scales (VAS) for measurement of appetite sensations, with and without a diet standardization prior to the test days.
On two different test days the subjects recorded their appetite sensations before breakfast and every 30 min during the 4.5 h postprandial period under exactly the same conditions.
55 healthy men (age 25.6+/-0.6 y, BMI 22.6+/-0.3 kg¿m2).
VAS were used to record hunger, satiety, fullness, prospective food consumption, desire to eat something fatty, salty, sweet or savoury, and palatability of the meals. Subsequently an ad libitum lunch was served and energy intake was recorded. Reproducibility was assessed by the coefficient of repeatability (CR) of fasting, mean 4.5 h and peak/nadir values.
CRs (range 20-61 mm) were larger for fasting and peak/nadir values compared with mean 4.5 h values. No parameter seemed to be improved by diet standardization. Using a paired design and a study power of 0.8, a difference of 10 mm on fasting and 5 mm on mean 4.5 h ratings can be detected with 18 subjects. When using desires to eat specific types of food or an unpaired design, more subjects are needed due to considerable variation. The best correlations of validity were found between 4.5 h mean VAS of the appetite parameters and subsequent energy intake (r=+/-0.50-0.53, P<0.001).
VAS scores are reliable for appetite research and do not seem to be influenced by prior diet standardization. However, consideration should be given to the specific parameters being measured, their sensitivity and study power. International Journal of Obesity (2000)24, 38-48
This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more artificial) conditions of the laboratory where the signal:noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a significantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably.
The purpose of present study was to compare the effects of moderate-load RE versus high-load on hunger response, blood lactate, glucose, and autonomic modulation in trained men, and to examine the correlations between these parameters. For this, eleven recreationally resistance trained males performed two randomized trials: moderate-load (6 sets at 70% 1RM and a 90 second rest interval between sets) and high-lo type (6 sets at 90% 1RM and a 180 second rest interval between sets) in the leg-press exercise until movement failure. The subjective rating of hunger was obtained through a visual analog scale. Glucose and lactate concentration were evaluated at rest, immediately after exercise, and 30 min post-exercise. Heart rate variability was recorded at baseline and during recovery (until 30 minutes after exercise) to assess autonomic modulation. The moderate-load condition induced lower subjective hunger ratings than the strength-type at post-0 (19.7±16.6 vs 47.3±27.7 mm), post-30 (33.6±22.9 vs 58.5±29.9 mm), and post-60 minutes after exercise (43.8±26.6 vs 67.8±27.9 mm)(p<0.05) and lower AUC hunger in relation to high-load (p< 0.006). Moderate-load RE presented greater lactate concentration and induced slower heart rate variability recovery in relation to high-load (p<0.05), but no difference was found in glucose, as well as no correlations between any of the variables investigated. In conclusion, moderate-load RE induced lower subjective hunger ratings, slower recovery of the parasympathetic nervous system, and higher lactate concentration in relation to high-load, but the metabolic variables were not correlated with hunger suppression.
The aim of this study was to compare the effect of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on sleep characteristics, appetite-related hormones, and eating behaviour. Eleven overweight, inactive men completed 2 consecutive nights of sleep assessments to determine baseline (BASE) sleep stages and arousals recorded by polysomnography (PSG). On separate afternoons (1400–1600 h), participants completed a 30-min exercise bout: either (i) MICE (60% peak oxygen consumption) or (ii) HIIE (60 s of work at 100% peak oxygen consumption: 240 s of rest at 50% peak oxygen consumption), in a randomised order. Measures included appetite-related hormones (acylated ghrelin, leptin, and peptide tyrosine tyrosine) and glucose before exercise, 30 min after exercise, and the next morning after exercise; PSG sleep stages; and actigraphy (sleep quantity and quality); in addition, self-reported sleep and food diaries were recorded until 48 h after exercise. There were no between-trial differences for time in bed (p = 0.19) or total sleep time (p = 0.99). After HIIE, stage N3 sleep was greater (21% ± 7%) compared with BASE (18% ± 7%; p = 0.02). In addition, the number of arousals during rapid eye movement sleep were lower after HIIE (7 ± 5) compared with BASE (11 ± 7; p = 0.05). Wake after sleep onset was lower following MICE (41 min) compared with BASE (56 min; p = 0.02). Acylated ghrelin was lower and glucose was higher at 30 min after HIIE when compared with MICE (p ≤ 0.05). There were no significant differences between conditions in terms of total energy intake (p ≥ 0.05). HIIE appears to be more beneficial than MICE for improving sleep quality and inducing favourable transient changes in appetite-related hormones in overweight, inactive men. However, energy intake was not altered regardless of exercise intensity.
Acute exercise transiently suppresses the orexigenic gut hormone acylated ghrelin, but the extent exercise intensity and duration determine this response is not fully understood. The effects of manipulating exercise intensity and duration on acylated ghrelin concentrations and hunger were examined in two experiments. In experiment one, nine healthy males completed three, 4-hour conditions (control, moderate-intensity running (MOD) and vigorous-intensity running (VIG)), with an energy expenditure of ~2.5 MJ induced in both MOD (55 min running at 52% peak oxygen uptake ( 2peak)) and VIG (36 min running at 75% 2peak). In experiment two, nine healthy males completed three, 9-hour conditions (control, 45 min running (EX45) and 90 min running (EX90)). Exercise was performed at 70% 2peak. In both experiments, participants consumed standardised meals, and acylated ghrelin concentrations and hunger were quantified at predetermined intervals. In experiment one, delta acylated ghrelin concentrations were lower than control in MOD (ES=0.44, P=0.01) and VIG (ES=0.98, P<0.001); VIG was lower than MOD (ES=0.54, P=0.003). Hunger ratings were similar across the conditions (P=0.35). In experiment two, delta acylated ghrelin concentrations were lower than control in EX45 (ES=0.77, P<0.001) and EX90 (ES=0.68, P<0.001); EX45 and EX90 were similar (ES=0.09, P=0.55). Hunger ratings were lower than control in EX45 (ES=0.20, P=0.01) and EX90 (ES=0.27, P=0.001); EX45 and EX90 were similar (ES=0.07, P=0.34). Hunger and delta acylated ghrelin concentrations remained suppressed at 1.5h in EX90 but not EX45. In conclusion, exercise intensity, and to a lesser extent duration, are determinants of the acylated ghrelin response to acute exercise.
Gut hormones send information about incoming nutrients to the rest of the body and thereby control many aspects of metabolism. The secretion of ghrelin and glucagon-like protein (GLP)-1, two hormones with opposite secretory patterns and opposite actions on multiple targets, is controlled by a limited number of G-protein coupled receptors (GPCRs); half of which recognize and bind dietary nutrient metabolites, metabolites generated by gut microbiota, and metabolites of the host's intermediary metabolism. Most metabolite GPCRs controlling ghrelin secretion are inhibitory, whereas all metabolite receptors controlling GLP-1 secretion are stimulatory. This dichotomy in metabolite sensor function, which is obtained through a combination of differential expression and cell-dependent signaling bias, offers pharmacological targets to stimulate GLP-1 and inhibit ghrelin through the same mechanism.
The aim of this study was to compare the effects of exercise intensity on appetite control: relative energy intake (energy intake minus the energy expenditure of exercise - REI), hunger scores, and appetite-regulating hormones in men and women. Eleven men and nine women were submitted to four experimental sessions: high-intensity intermittent all out exercise (HIIE-A) 60x 8s interspersed by 12s of passive recovery; high-intensity intermittent exercise (HIIE) at 100% of maximal load attained in incremental test; steady state exercise at 60% of maximal load, matched by work done, and a control session. Exercise was performed 1.5h after a standardized breakfast, and an ad libitum lunch was offered 4h after breakfast. Blood concentration of insulin, cortisol, acylated ghrelin, peptideYY3-36, glucose and hunger scores were measured when fasting, and at 1.5, 2, 3.25 and 4h of experiment. REI was lower in all exercises than in the control, without differences between exercises and sex showing no compensation in energy intake due to any exercise; the hunger scores were lower only in the exercises performed at higher intensity (HIIE and HIIE-A) compared to the control. The area under the curve of acylated ghrelin was lower in the HIIE-A when compared to the control. PeptideYY3-36 was higher in men than women and cortisol higher in women than men independently of the condition. Although high-intensity exercises promoted a little more pronounced effects in the direction of supressing the appetite, no differences were observed in REI, demonstrating that these modifications were not sufficient to affect energy intake.
Acute bouts of high-intensity exercise modulate peripheral appetite regulating hormones to transiently suppress hunger. However, the effects of physical activity on central appetite regulation have yet to be fully investigated.
We used functional magnetic resonance imaging (fMRI) to compare neural responses to visual food stimuli after intense exercise and rest.
Fifteen lean healthy men (mean ± SD age: 22.5 ± 3.1 y; mean ± SD body mass index: 24.2 ± 2.4 kg/m(2)) completed two 60-min trials-exercise (EX; running at ∼70% maximum aerobic capacity) and a resting control trial (REST)-in a counterbalanced order. After each trial, an fMRI assessment was completed in which images of high- and low-calorie foods were viewed.
EX significantly suppressed subjective appetite responses while increasing thirst and core-body temperature. Furthermore, EX significantly suppressed ghrelin concentrations and significantly enhanced peptide YY release. Neural responses to images of high-calorie foods significantly increased dorsolateral prefrontal cortex activation and suppressed orbitofrontal cortex (OFC) and hippocampus activation after EX compared with REST. After EX, low-calorie food images increased insula and putamen activation and reduced OFC activation compared with REST. Furthermore, left pallidum activity was significantly elevated after EX when low-calorie images were viewed and was suppressed when high-calorie images were viewed, and these responses correlated significantly with thirst.
Exercise increases neural responses in reward-related regions of the brain in response to images of low-calorie foods and suppresses activation during the viewing of high-calorie foods. These central responses are associated with exercise-induced changes in peripheral signals related to appetite-regulation and hydration status. This trial was registered at www.clinicaltrials.gov as NCT01926431.
This study examined the effects of an acute bout of exercise of low-intensity on food intake and energy expenditure over four days in women taking oral contraceptives. Twenty healthy, active (n=10) and inactive (n=10) pre-menopausal women taking oral contraceptives completed two conditions (exercise and control), in a randomised, crossover fashion. The exercise experimental day involved cycling for one hour at an intensity equivalent to 50% of maximum oxygen uptake and two hours of rest. The control condition comprised three hours of rest. Participants arrived at the laboratory fasted overnight; breakfast was standardised and an ad libitum pasta lunch was consumed on each experimental day. Participants kept a food diary to measure food intake and wore an Actiheart to measure energy expenditure for the remainder of the experimental days and over the subsequent 3 days. There was a condition effect for absolute energy intake (exercise vs. control: 3363 ± 668 kJ vs. 3035 ± 752 kJ; p = 0.033, d = 0.49) and relative energy intake (exercise vs. control: 2019 ± 746 kJ vs. 2710 ± 712 kJ; p < 0.001, d = -1.00) at the ad libitum lunch. There were no significant differences in energy intake over the four days in active participants and there was a suppression of energy intake on the first day after the exercise experimental day compared with the same day of the control condition in inactive participants (mean difference = -1974 kJ; 95% CI -1048 to -2900 kJ, p = 0.002, d = -0.89). There was a group effect (p = 0.001, d = 1.63) for free-living energy expenditure, indicating that active participants expended more energy than inactive participants during this period. However, there were no compensatory changes in daily physical activity energy expenditure. These results support the use of low-intensity aerobic exercise as a method to induce a short-term negative energy balance in inactive women taking oral contraceptives.
Copyright © 2015. Published by Elsevier Ltd.
Oral ingestion of sodium bicarbonate (bicarbonate loading) has acute ergogenic effects on short-duration, high-intensity exercise. Because sodium bicarbonate is 27% sodium, ergogenic doses (ie, 300 mg∙kg(-1)) result in sodium intakes well above the Dietary Reference Intakes upper limit of 2300 mg/day. Therefore, it is conceivable that bicarbonate loading could have hypertensive effects. Therefore, we performed a double-blind crossover trial to evaluate the hypothesis that bicarbonate loading increases resting and exercise blood pressure (BP). A secondary hypothesis was that bicarbonate loading causes gastrointestinal distress. Eleven endurance-trained men and women (exercise frequency, 4.6 ± 0.4 sessions/wk; duration, 65 ± 6 min/session) underwent testing on two occasions in random sequence: once after bicarbonate loading (300 mg∙kg(-1)) and once after placebo ingestion. BP and heart rate were measured before bicarbonate or placebo consumption, 30 minutes after consumption, during 20 min of steady state submaximal cycling exercise, and during recovery. Bicarbonate loading did not affect systolic BP during rest, exercise, or recovery (P = .38 for main treatment effect). However, it resulted in modestly higher diastolic BP (main treatment effect, +3.3 ± 1.1 mmHg, P = .01) and higher heart rate (main treatment effect, +10.1 ± 2.4 beats per minute, P = .002). Global ratings of gastrointestinal distress severity (0-10 scale) were greater after bicarbonate ingestion (5.1 ± 0.5 vs 0.5 ± 0.2, P < .0001). Furthermore, 10 of the 11 subjects (91%) experienced diarrhea, 64% experience bloating and thirst, and 45% experienced nausea after bicarbonate loading. In conclusion, although a single, ergogenic dose of sodium bicarbonate does not appear to have acute, clinically important effects on resting or exercise BP, it does cause substantial gastrointestinal distress.
Our understanding of the regulation of appetite has improved considerably over the last few decades. Recent work, stimulated by efforts aimed at curbing the current obesity epidemic, has unravelled some of the complex pathways regulating energy homeostasis. Key factors to this progress have been the discovery of leptin and the neuronal circuitry involved in mediating its effects, as well as the identification of gut hormones that have important physiological roles relating to energy homeostasis. Despite these advances in research, there are currently no effective treatments for the growing problem of obesity. In this article, we summarise the regulatory pathways controlling appetite with a special focus on gut hormones. We detail how recent findings have contributed to our knowledge regarding the pathogenesis and treatment of common obesity. A number of barriers still need to be overcome to develop safe and effective anti-obesity treatments. We outline problems highlighted by historical failures and discuss the potential of augmenting natural satiety signals, such as gut hormones, to treat obesity.International Journal of Obesity advance online publication, 19 June 2012; doi:10.1038/ijo.2012.93.
This article reviews the regulation of appetite from a biopsychological perspective. It considers psychological experiences and peripheral nutritional systems (both episodic and tonic) and addresses their relationship with the CNS networks that process and integrate their input. Whilst such regulatory aspects of obesity focus on homeostatic control mechanisms, in the modern environment hedonic aspects of appetite are also critical. Enhanced knowledge of the complexity of appetite regulation and the mechanisms that sustain obesity indicate the challenge presented by management of the obesity epidemic. Nonetheless, effective control of appetite expression remains a critical therapeutic target for weight management. Currently, strategies which utilise a combination of agents to target both homeostatic and hedonic control mechanisms represent the most promising approaches. This article is part of a Special Issue entitled 'Central Control of Food Intake'.
Ingestion of agents that modify blood buffering action may affect high-intensity performance. Here we present a meta-analysis of the effects of acute ingestion of three such agents - sodium bicarbonate, sodium citrate and ammonium chloride - on performance and related physiological variables (blood bicarbonate, pH and lactate). A literature search yielded 59 useable studies with 188 observations of performance effects. To perform the mixed-model meta-analysis, all performance effects were converted into a percentage change in mean power and were weighted using standard errors derived from exact p-values, confidence limits (CLs) or estimated errors of measurement. The fixed effects in the meta-analytic model included the number of performance-test bouts (linear), test duration (log linear), blinding (yes/no), competitive status (athlete/nonathlete) and sex (male/female). Dose expressed as buffering mmoL/kg/body mass (BM) was included as a strictly proportional linear effect interacted with all effects except blinding. Probabilistic inferences were derived with reference to thresholds for small and moderate effects on performance of 0.5% and 1.5%, respectively. Publication bias was reduced by excluding study estimates with a standard error >2.7%. The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly moderate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 3.5 mmoL/kg/BM (∼0.3 g/kg/BM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of 1.5 mmoL/kg/BM (∼0.5 g/kg/BM) had an unclear effect on performance of 0.0% (±1.3%), while the five studies and six estimates for ammonium chloride produced a possibly moderate impairment of 1.6% (±1.9%) with a typical dose of 5.5 mmoL/kg/BM (∼0.3 g/kg/BM). Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1 mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (±1.1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ±1.2%. The only noteworthy effects involving physiological variables were a small correlation between performance and pre-exercise increase in blood bicarbonate with sodium bicarbonate ingestion, and a very large correlation between the increase in blood bicarbonate and time between sodium citrate ingestion and exercise. The approximate equal and opposite effects of sodium bicarbonate and ammonium chloride are consistent with direct performance effects of pH, but sodium citrate appears to have some additional metabolic inhibitory effect. Important future research includes studies of sodium citrate ingestion several hours before exercise and quantification of gastrointestinal symptoms with sodium bicarbonate and citrate. Although individual responses may vary, we recommend ingestion of 0.3-0.5 g/kg/BM sodium bicarbonate to improve mean power by 1.7% (±2.0%) in high-intensity races of short duration.
There is growing interest in the effects of exercise on plasma gut hormone levels and subsequent energy intake (EI) but the effects of mode and exercise intensity on anorectic hormone profiles on subsequent EI remain to be elucidated. We aimed to investigate whether circulating peptide YY(3-36) (PYY(3-36)) and glucagon-like peptide-1 (GLP-1 or GCG as listed in the HUGO Database) levels depend on exercise intensity, which could affect subsequent EI. Ten young male subjects (mean+/-s.d., age: 23.4+/-4.3 years, body mass index: 22.5+/-1.0 kg/m(2), and maximum oxygen uptake (VO(2 max)): 45.9+/-8.5 ml/kg per min) received a standardized breakfast, which was followed by constant cycling exercise at 75% VO(2 max) (high intensity session), 50% VO(2 max) (moderate intensity session), or rest (resting session) for 30 min. At lunch, a test meal was presented, and EI was calculated. Blood samples were obtained during three sessions for measurements of glucose, insulin, PYY(3-36), and GLP-1, which includes GLP-1 (7-36) amide and GLP-1 (9-36) amide. Increases in blood PYY(3-36) levels were dependent on the exercise intensity (effect of session: P<0.001 by two-way ANOVA), whereas those in GLP-1 levels were similar between two different exercise sessions. Of note, increase in area under the curve values for GLP-1 levels was negatively correlated with decrease in the EI in each exercise session (high: P<0.001, moderate: P=0.002). The present findings raise the possibility that each gut hormone exhibits its specific blood kinetics in response to two different intensities of exercise stimuli and might play differential roles in regulation of EI after exercise.
During exercise, the oxygen consumption above which aerobic energy production is supplemented by anaerobic mechanisms, and which results in a significant increase in lactate, is termed the anaerobic threshold (AT). This power output has important functional implications because it is a demarcation of the work rate above which metabolic acidosis accelerates the stimulation to breathing, and exercise endurance becomes reduced. The justification for relating lactate increase to tissue anaerobiosis during exercise is presented, and the gas exchange methods for measuring the AT are described. The form of work affects the AT, treadmill being about 10% greater than cycling in sedentary subjects. It is useful for predicting the ability of the subject to sustain a given work rate for a prolonged period and for determining the VO2 above which there is cardiovascular insufficiency in meeting tissue O2 requirements.
To examine the effects of exercise on short term energy intake and to investigate the existence of exercise-induced anorexia.
Two studies were conducted, both with three treatment conditions and employing a repeated measures design.
The Human Appetite Research Unit at Leeds University Psychology department.
Twenty three healthy, lean male subjects (n = 11 and n = 12 respectively) were recruited from the student/staff population of Leeds University.
Subjects were randomly assigned to a control, low intensity and high intensity exercise treatment in the first study and to a control, short duration and long duration exercise treatment (high intensity) in the second. Motivation to eat was measured by visual analogue rating scales and by the length of the time between the end of exercise and the volitional onset of eating. Energy and macronutrient intakes were measured by means of a free-selection test meal and by recorded intakes for the next 2 days.
Subjective feelings of hunger were significantly suppressed during and after intense exercise sessions (P 0.01), but the suppression was short-lived. Exercise sessions had no significant effect on the total amount of food consumed in the test meal but intense exercise delayed the start of eating (P < 0.05). When energy intake was assessed relative to the energy expended during the exercise or control periods, only the long duration, high intensity session created a significant short-term negative energy balance (P < 0.001).
These studies indicate that exercise-induced anorexia can be characterized by a brief suppression of hunger, accompanied by a delay to the onset of eating. The temporal aspects of exercise-induced anorexia may best be measured by the resistance to begin eating rather than the amount of food consumed.
Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.