Energy balance and obesity: the emerging role of glucagon like peptide-1 receptor agonists.

PURPOSE OF REVIEW: With obesity affecting over one billion people globally, understanding and managing this complex condition is more crucial than ever. This review explores the emerging role of GLP-1 receptor agonists (GLP-1RA) in weight management, focusing on their impact on energy balance. It highlights the necessity of this investigation due to the limited knowledge on both the short-term and long-term implications of GLP-1RA on energy expenditure (EE) and energy intake (EI). RECENT FINDINGS: GLP-1RA, such as liraglutide and semaglutide, have shown significant efficacy in promoting weight loss by reducing appetite, cravings and consequently, EI. Newer medications such as tirzepatide have demonstrated even greater weight loss success. Emerging evidence also suggests potential effects on EE, which could explain the greater weight loss success achieved with GLP-1 RA rather than typical lifestyle changes. However, comprehensive data on the total impact of these drugs on energy balance remain limited. SUMMARY: The findings underscore the promising role of GLP-1RA in obesity management, particularly through mechanisms influencing both EI and EE. Future research should focus on systematically measuring all components of energy balance to fully elucidate the mechanisms of GLP-1RA and optimize their therapeutic use for personalized medicine.

Effects of 2 months of methylphenidate on energy expenditure in individuals with obesity: A randomized, double-blind, placebo-controlled pilot study.

Methylphenidate (MPH) has been previously shown to increase resting energy expenditure (REE) in individuals of normal weight; however, the effects on individuals living with obesity are currently unknown. Ten individuals living with obesity were randomly assigned to undergo 60 days of MPH administration with a daily dose of 0.5 mg/kg body weight or a placebo control. REE was measured before and after the 60-day intervention. There was a trend toward significance for group × time interaction on REE (p = 0.082) with a large effect size (η2 = 0.331), with MPH administration increasing REE compared to a decrease in placebo control. Preliminary findings from this pilot study show that MPH has the potential to counter the adaptive thermogenic process commonly seen in weight loss. This is a unique finding among pharmacotherapies, as no approved obesity drugs measurably impact REE.

Appetite Changes in Weight Regain and Weight Maintenance After Roux-en-Y Gastric Bypass.

PURPOSE: Roux-en-Y gastric bypass (RYGB) surgery produces significant weight loss. However, a number of patients experience weight regain years after surgery. Factors driving weight regain after surgical interventions are currently being explored. Our objective was to investigate appetite-related measures associated with weight regain after RYGB surgery. MATERIALS AND METHODS: Using a cross-sectional design, 29 participants (49.6 ± 9.1 years of age; current BMI 32.4 ± 4.7 kg/m2, 43.6 ± 8.9 months post-RYGB) were stratified into tertiles according to weight regain per month after nadir (weight maintenance (WM), n = 9; low weight regain (LWR), n = 10; and high weight regain (HWR), n = 10). The average weight regain was, by design, significantly different between the groups (WM = 2.2 ± 2.5 kg; LWR = 10.0 ± 3.4 kg; HWR = 14.9 ± 6.3 kg regained, p < 0.05). Appetite (visual analog scales), olfactory performance ("sniffin sticks"), eating behaviors (Three Factor Eating Questionnaire), food reward (Leeds Food Preference Questionnaire), and appetite-related hormones (ghrelin, PYY, GLP-1 and leptin) were measured fasting and in response to a standardized test meal. RESULTS: Dietary restraint was significantly higher than clinical cutoffs in WM and LWR (p < 0.05). As expected, significant time effects were noted for ghrelin, PYY, and GLP-1, but there were no group differences. CONCLUSION: The results suggest that appetite-related outcomes are similar across individuals who have maintained weight loss and experienced regain following RYGB.

Circulating small extracellular vesicles increase after an acute bout of moderate-intensity exercise in pregnant compared to non-pregnant women.

The physiological and molecular mechanisms linking prenatal physical activity and improvements in maternal-fetal health are unknown. It is hypothesized that small extracellular vesicles (EVs, ~ 10-120 nm) are involved in tissue cross-talk during exercise. We aimed to characterize the circulating small EV profile of pregnant versus non-pregnant women after an acute bout of moderate-intensity exercise. Pregnant (N = 10) and non-pregnant control (N = 9) women performed a single session of moderate-intensity treadmill walking for 30 min. Plasma was collected immediately pre- and post-exercise, and small EVs were isolated by differential ultracentrifugation. EV presence was confirmed by western blotting for the small EV proteins TSG-101 and flottilin-1. Small EVs were quantified by size and concentration using nanoparticle tracking analysis and transmission electron microscopy. All EV fractions were positive for TSG-101 and flotillin-1, and negative for calnexin. Mean vesicle size at baseline and percent change in size post-exercise were not different between groups. At baseline, pregnant women had higher levels of small EVs compared to controls (1.83E+10 ± 1.25E+10 particles/mL vs. 8.11E+09 ± 4.04E+09 particles/mL, respectively; p = 0.032). Post-exercise, small EVs increased significantly in the circulation of pregnant compared to non-pregnant women after correcting for baseline values (64.7 ± 24.6% vs. - 23.3 ± 26.1%, respectively; F = 5.305, p = 0.035). Further research is needed to assess the functional roles of exercise-induced small EVs in pregnancy.

Humans in the cold: Regulating energy balance.

For humans to maintain a stable core temperature in cold environments, an increase in energy expenditure (EE) is required. However, little is known about how cold stimulus impacts energy balance as a whole, as energy intake (EI) has been largely overlooked. This review focuses on the current state of knowledge regarding how cold exposure (CE) impacts both EE and EI, while highlighting key gaps and shortcomings in the literature. Animal models clearly reveal that CE produces large increases in EE, while decreasing environmental temperatures results in a significant negative dose-response effect in EI (r=-.787, P<.001), meaning animals eat more as temperature decreases. In humans, multiple methods are used to administer cold stimuli, which result in consistent yet quantitatively small increases in EE. However, only two studies have measured ad libitum food intake in combination with acute CE in humans. Chronic CE (i.e., cold acclimation) studies have been shown to produce minimal changes in body weight, with an average compensation of ~126%. Although more studies are required to investigate how cold impacts EI in humans, results presented in this review warrant caution before presenting or considering CE as a potential adjunct to weight loss strategies.

Examination of the Myokine Response in Pregnant and Non-pregnant Women Following an Acute Bout of Moderate-Intensity Walking.

BACKGROUND: It is recommended that women accumulate 150-min of weekly moderate-intensity physical activity (MPA) when pregnant. Engaging in regular physical activity (PA) confers many health benefits to both the mother and the fetus. However, the molecular mechanisms by which these health benefits are bestowed are not well understood. One potential factor that may be contributing to the observed benefits is myokines, which are small peptides secreted by skeletal muscles. In the non-pregnant population, myokines are believed to be involved in the molecular mechanisms resulting from PA. The objective of this study was to characterize and compare the myokine profile of pregnant and non-pregnant women, after an acute bout of MPA. METHODS: Pregnant (n = 13) and non-pregnant (n = 17) women were recruited from the Ottawa region to undergo a treadmill walking session at moderate-intensity (40-60% heart rate reserve). Pre- and post-exercise serum samples were taken, and a set of 15 myokines were analyzed although only 10 were detected. IL-6 was analyzed using a high-sensitivity assay, while FGF21, EPO, BDNF, Fractalkine, IL-15, SPARC, FABP-3, FSTL-1, and oncostatin were analyzed using various multiplex assays. RESULTS: The pregnant and non-pregnant groups did not differ in terms of age, height, non/pre-pregnancy weight, BMI, and resting heart rate. Baseline levels of EPO and oncostatin were higher in the pregnant group while FGF21 was higher in the non-pregnant group. Circulating levels of three myokines, FGF21, EPO, and IL-15 significantly increased in response to the acute exercise in the pregnant group. Non-pregnant women exhibited an increase in three myokines, FABP-3, FSTL-1, and oncostatin, while one myokine, EPO, decreased post-exercise. SPARC, fractalkine and BDNF were shown to increase post-exercise regardless of pregnancy status while the response for BDNF was more pronounced in the non-pregnant group. CONCLUSION: This is the first study examining myokine response following an acute bout of PA in pregnancy. Moderate intensity PA, which is recommended during pregnancy, elicited an increase in four myokines post-compared to pre-exercise in the pregnant group. Further research is warranted to understand the role of myokines in pregnancy.