Meal-related changes in ghrelin, peptide YY, and appetite in normal weight and overweight children

Objective: Ghrelin and peptide YY (PYY) are two gut hormones that have effects on appetite. Our objectives were to characterize the patterns of secretion of these hormones in response to feeding in school‐age children and determine whether there were differences between normal weight (NW) and overweight (OW) subjects. Methods and Procedures: This was a cross‐sectional study at one tertiary care center. Subjects were 7‐ to 11‐year‐old healthy NW and OW volunteers recruited from local advertisements. Following an overnight fast, the subjects were given a standardized breakfast and lunch and had nine hourly blood samples for total ghrelin and total PYY. We assessed whether ghrelin and PYY levels changed from the preprandial to postprandial state and corresponded to reported hunger/satiety. Results: Hunger ratings were similar between the two groups throughout the study period. Ghrelin was not suppressed after eating, did not rise prior to the next meal, and did not correspond to hunger ratings in either group. PYY increased postprandially and decreased preprandially in the NW group, but OW children exhibited this pattern for only part of the day. PYY levels incompletely corresponded to reported satiety in the OW group. Discussion: Mixed meal consumption had little effect on ghrelin secretion and a variable effect on PYY secretion in young children in our study. Differences that were observed between the groups do not suggest that an abnormality in their secretion contributes to the development of obesity.     

Meal timing and composition influence ghrelin levels, appetite scores and weight loss maintenance in overweight and obese adults

BackgroundAlthough dietary restriction often results in initial weight loss, the majority of obese dieters fail to maintain their reduced weight. Diet-induced weight loss results in compensatory increase of hunger, craving and decreased ghrelin suppression that encourage weight regain. A high protein and carbohydrate breakfast may overcome these compensatory changes and prevent obesity relapse.MethodsIn this study 193 obese (BMI 32.2 ± 1.0 kg/m²), sedentary non diabetic adult men and women (47 ± 7 years) were randomized to a low carbohydrate breakfast (LCb) or an isocaloric diet with high carbohydrate and protein breakfast (HCPb). Anthropometric measures were assessed every 4 weeks. Fasting glucose, insulin, ghrelin, lipids, craving scores and breakfast meal challenge assessing hunger, satiety, insulin and ghrelin responses, were performed at baseline, after a Diet Intervention Period (Week 16) and after a Follow-up Period (Week 32).ResultsAt Week 16, groups exhibited similar weight loss: 15.1 ± 1.9 kg in LCb group vs. 13.5 ± 2.3 kg in HCPb group, p = 0.11. From Week 16 to Week 32, LCb group regained 11.6 ± 2.6 kg, while the HCPb group lost additional 6.9 ± 1.7 kg. Ghrelin levels were reduced after breakfast by 45.2% and 29.5% following the HCPb and LCb, respectively. Satiety was significantly improved and hunger and craving scores significantly reduced in the HCPb group vs. the LCb group.ConclusionA high carbohydrate and protein breakfast may prevent weight regain by reducing diet-induced compensatory changes in hunger, cravings and ghrelin suppression. To achieve long-term weight loss, meal timing and macronutrient composition must counteract these compensatory mechanisms which encourage weight regain after weight loss.     

Dehydroepiandrosterone concentration in adipose tissue of normal and overweight subjects.

Unconjugated dehydroepiandrosterone has been isolated from human abdominal adipose tissue and identified by double isotope derivatization and recrystallization to constant isotope ratio. Gas chromatography with electron capture detection revealed an actual dehydroepiandrosterone concentration between 0.32 to 2.82 mug/g in adipose tissue of normal and overweight subjects. The approximate dehydroepiandrosterone content of the total adipose tissue mass varied between 30 and 173 mg in subjects with severe obesity.     

Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects.

Oral glucose is a potent stimulant of glucagon-like peptide-1 (GLP-1) secretion. The effect of oral fructose on GLP-1 secretion in humans is unknown. The aims of this study were to determine (i) whether oral fructose stimulates GLP-1 secretion and (ii) the comparative effects of oral glucose and fructose on appetite. On 3 separate days, 8 fasting healthy males received, in single-blind randomized order (i) 75 g glucose, (ii) 75 fructose, or (iii) 75 g glucose followed by 75 g fructose I h later. Venous glucose, insulin and GLP-1 were measured. Appetite was assessed by visual analog questionnaires and intake of a buffet meal. Whereas glucose and fructose both increased plasma glucose, insulin and GLP-1 (P < 0.000)] for all), the response to glucose was much greater (P < 0.005 for all). There was no increase in plasma GLP-1 when fructose was given after glucose. There was no difference in food intake after oral glucose or fructose. We conclude that oral fructose (75 g) stimulates GLP-1 (and insulin) secretion, but the response is less than that to 75 g glucose. These observations suggest that neither GLP-1 nor insulin play a major role in the regulation of satiation.     

Effect of weight loss on P wave dispersion in obese subjects

Objective: The aim of this study was to investigate effect of loss weight on P wave dispersion in obese subjects. Research Methods and Procedures: After a 12‐week weight loss program (diet and medical therapy), a total of 30 (24 women and six men) obese subjects who had lost at least 10% of their original weight were included in the present study. All subjects underwent a routine standard 12‐lead surface electrocardiogram. Electrocardiograms were transferred to a personal computer by a scanner and then magnified 400 times by Adobe Photoshop software (Adobe Systems, Mountain View, CA). P wave dispersion, which is also defined as the difference between the maximum P wave duration and the minimum P wave duration, was also calculated. Results: After a 12‐week weight loss program, BMI (p < 0.001), maximum P wave duration (p < 0.001), and P wave dispersion (p < 0.001) significantly decreased. The mean percentage of weight loss was 13% (10% to 20.3%). The decrease in the level of P wave dispersion (21 ± 10 and 7 ± 12 ms, p < 0.002) was more prominent in Group II (≥12% loss of their original weight) than Group I (<12% loss of their original weight) after the weight loss program. A statistically significant correlation between decrease in the level of P wave dispersion and percentage of weight loss was found (r = 0.624, p < 0.001). Discussion: Substantial weight loss in obese subjects is associated with a decrease of P wave duration and dispersion. Therefore, these observations suggest that substantial weight loss is associated with improvement in atrial repolarization abnormalities in obese subjects.     

Effect of weight loss on lactate transporter expression in skeletal muscle of obese subjects.

The effects of weight loss on skeletal muscle lactate transporter [monocarboxylate transporter (MCT)] expression in obese subjects were investigated to better understand how lactate transporter metabolism is regulated in insulin-resistant states. Ten obese subjects underwent non-macronutrient-specific energy restriction for 15 wk. Anthropometric measurements and a needle biopsy of the vastus lateralis muscle before and after the weight loss program were performed. Enzymatic activity, fiber type distribution, and skeletal muscle MCT protein expression were measured. Muscle from nonobese control subjects was used for comparison of MCT levels. The program induced a weight loss of 9.2 +/- 1.6 kg. Compared with controls, muscle from obese subjects showed a strong tendency (P = 0.06) for elevated MCT4 expression (+69%) before the weight loss program. MCT4 expression decreased (-7%) following weight loss to reach levels that were not statistically different from control levels. There were no differences in MCT1 expression between controls and obese subjects before and after weight loss. A highly predictive regression model (R2 = 0.93), including waist circumference, citrate synthase activity, and percentage of type 1 fibers, was found to explain the highly variable MCT1 response to weight loss in the obese group. Therefore, in obesity, MCT1 expression appears linked both to changes in oxidative parameters and to changes in visceral adipose tissue content. The strong tendency for elevated expression of muscle MCT4 could reflect the need to release greater amounts of muscle lactate in the obese state, a situation that would be normalized with weight loss as indicated by decreased MCT4 levels.     

Effect of weight loss on muscle lipid content in morbidly obese subjects

The purpose of this study was to test the hypothesis that weight loss results in a reduction in intramuscular lipid (IMCL) content that is concomitant with enhanced insulin action. Muscle biopsies were obtained from morbidly obese individuals [body mass index (BMI) 52.2 +/- 2.5 kg/m(2); n = 6] before and after gastric bypass surgery, an intervention that improves insulin action. With intervention, there was a 47% reduction (P < 0.01) in BMI and a 93% decrease in homeostasis model assessment, or HOMA (7.0 +/- 1.9 vs. 0.5 +/- 0.1). Histochemically determined IMCL content decreased (P < 0.05) by approximately 30%. In relation to fiber type, IMCL was significantly higher in type I vs. type II fibers. In both fiber types, there were reductions in IMCL and trends for muscle atrophy. Despite these two negating factors, the IMCL-to-fiber area ratio still decreased by approximately 44% with weight loss. In conclusion, despite differing initial levels and possible atrophy, weight loss appears to decrease IMCL deposition to a similar relative extent in type I and II muscle fibers. This reduction in intramuscular triglyceride may contribute to enhanced insulin action seen with weight loss.     

Effect of the timing of weight cycling during adulthood on mortality risk in overweight and obese postmenopausal women

Inconsistent results exist for whether or not weight cycling (WgtC) and weight variability (WgtV) increase mortality risk. The aim of this study was to examine the effect of WgtC and WgtV during adulthood on mortality risk. Data was obtained from the Women's Health Initiative (WHI) observational study (OS) dataset, acquired from the National Heart, Lung and Blood Institute (N = 47,473 overweight and obese women; age 50–79 years). Women were categorized (stable; WgtV: weight‐gainer or loser; or WgtC) based on weight changes during early (18–35 years), mid (35–50 years), and late (50 years to current age) adulthood. Those with weight changes of <5% during all three time‐periods were classified as being stable‐weight. Weight‐gainers were those with at least one period of weight‐gain (≥5%) without a period of weight‐loss (≥5%), and weight‐losers were those with at least one period of loss without a period of gain during all time‐periods. Those who experienced both a period of weight‐gain and loss (≥5%) were categorized as WgtC. Compared to stable‐weight individuals, WgtC and WgtV across adulthood were not significantly associated with mortality risk when the age‐period of weight change was not considered. However, when considering the age period, increased mortality risk was observed for every 5 kg of weight‐gain during early (hazard ratio (HR) = 1.04 (1.00–1.07)) or mid‐adulthood (HR = 1.05 (1.02–1.08)), or for every 5 kg of weight‐loss since mid (HR = 1.12 (1.01–1.24)) or late‐adulthood (HR = 1.12 (1.04–1.20)). In conclusion, merely investigating WgtC and WgtV by weight changes across adulthood may not be sufficient to fully describe mortality risk, and the age at which the weight change occurred might be as important to consider.     

GLP-1 and appetite responses to a meal in lean and overweight adolescents following exercise

Objective: Increased physical activity is an integral part of weight loss programs in adolescents. We prospectively investigated the effects of exercise on glucagon‐like peptide‐1 (GLP‐1) concentrations and on appetite markers. Methods and Procedures: Normal weight (NW) and at risk of overweight/overweight (OW) male adolescents (n = 17/gr) underwent five consecutive days of aerobic exercise (1 h/day). A test meal was administered prior to the first exercise session and 36 hours following the last exercise session. GLP‐1 and markers of appetite were assessed. Results: GLP‐1 concentrations over the course of the test meal were lower in OW compared to NW boys (P < 0.05), while fasting GLP‐1 concentrations tended to be lower in OW boys (0.05 < P < 0.1). Exercise caused an increase in the acute GLP‐1 response to the liquid meal (from 52 to 78%, P = 0.02) that was similar in NW and OW adolescents. OW adolescents expressed greater restraint compared to NW adolescents (three‐factor eating questionnaire, TFEQ) and there was a significant correlation between TFEQ for restraint score and BMI s.d. both before and after exercise intervention (P < 0.015). There was no significant correlation between markers of appetite and GLP‐1 concentrations. Discussion: Lower concentrations of GLP‐1, a satiety hormone, in OW compared to NW male adolescents support the theory that GLP‐1 plays a role in the etiology of overweight. Whether the greater meal‐induced, 0–30 min GLP‐1 response following exercise is associated with increased satiety, a potentially beneficial effect of exercise, needs to be evaluated in larger studies.     

Adipocyte triglyceride turnover and lipolysis in lean and overweight subjects

Human obesity is associated with decreased triglyceride turnover and impaired lipolysis in adipocytes. We determined whether such defects also occur in subjects with only moderate increase in fat mass. Human abdominal subcutaneous adipose tissue was investigated in healthy, nonobese subjects [body mass index (BMI) > 17 kg/m² and BMI < 30 kg/m²]. Triglyceride age, reflecting lipid turnover, was examined in 41 subjects by assessing the incorporation of atmospheric ¹⁴C into adipose lipids. Adipocyte lipolysis was examined as the ability of lipolytic agents to stimulate glycerol release in 333 subjects. Adipocyte triglyceride age was markedly increased in overweight (BMI ≥ 25 kg/m²) compared with lean subjects (P = 0.017) with triglyceride T_1/2 of 14 and 9 months, respectively (P = 0.04). Triglyceride age correlated positively with BMI (P = 0.002) but not with adipocyte volume (P = 0.2). Noradrenaline-, isoprenaline- or dibutyryl cyclic AMP-induced lipolysis was inversely correlated with triglyceride age (P < 0.01) and BMI (P < 0.0001) independently of basal lipolysis, gender, and nicotine use. Current, but not the highest or lowest BMI in adult life, correlated significantly (inversely) with lipolysis. In conclusion, adipocyte triglyceride turnover and lipolytic activity are decreased in overweight subjects and reflect the current BMI status. These changes may confer an increased risk for early development and/or maintenance of excess body fat.