Benjamin Buemann

The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction

BACKGROUND: Previous studies have indicated that the secretion of the intestinal satiety hormone glucagon-like peptide-1 (GLP-1) is attenuated in obese subjects.OBJECTIVE: To compare meal-induced response of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in obese and lean male subjects, to investigate the effect of a major weight reduction in the obese subjects, and to look for an association between these hormones and ad libitum food intake.METHOD: Plasma concentrations of intestinal hormones and appetite sensations were measured prior to, and every 30 min for 180 min after, ingestion of a 2.5 MJ solid test meal. Gastric emptying was estimated scintigraphically. An ad libitum lunch was served 3 h after the test meal.SUBJECTS: Nineteen non-diabetic obese (body mass index (BMI) 34.1–43.8 kg/m2) and 12 lean (BMI 20.4–24.7 kg/m2) males. All obese subjects were re-examined after a mean stabilised weight loss of 18.8 kg (95% CI 14.4–23.2).RESULTS: Total area under the GLP-1 response curve (AUCtotal, GLP-1) was lower in obese before and after the weight loss compared to lean subjects (P<0.05), although weight loss improved the response from 80 to 88% of that of the lean subjects (P=0.003). The GIP response was similar in obese and lean subjects. However, after the weight loss both AUCtotal, GIP and AUCincremental, GIP were lowered (P<0.05). An inverse correlation was observed between AUCincremental, GIP and energy intake at the subsequent ad libitum meal in all groups. In lean subjects ad libitum energy intake was largely predicted by the insulin response to the preceding meal (r 2=0.67, P=0.001).CONCLUSION: Our study confirmed previous findings of a reduced postprandial GLP-1 response in severely obese subjects. Following weight reduction, GLP-1 response in the obese subjects apparently rose to a level between that of obese and lean subjects. The data suggests that postprandial insulin and GIP responses are key players in short-term appetite regulation.

Effect of obesity and major weight reduction on gastric emptying.

BACKGROUND: An enhanced gastric emptying rate might reduce the satiating effect of food and thereby promote obesity. Gastric emptying rate has previously been compared between obese and lean subjects with conflicting outcome.OBJECTIVE: Comparison of gastric emptying rate in lean and obese subjects before and after a major weight reduction.DESIGN: The study was designed as a case–control study comparing obese and lean subjects and a subsequent comparison of obese subjects before and after a dietary induced major weight reduction.METHOD: Gastric emptying rate following a solid test meal was estimated scintigraphically for 3 h using the left anterior oblique projection.SUBJECTS: Nineteen non-diabetic obese (mean BMI=38.7 kg/m2) and 12 lean (mean BMI=23.1 kg/m2) males matched for age and height. All obese subjects were re-examined after a mean weight loss of 18.8 kg (95% CI, 14.4–23.2) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability.RESULTS: When comparing obese and lean subjects no differences were seen in overall 3 h emptying rate (30.3% per hour vs 30.5% per hour). However, a trend towards a higher percentage gastric emptying during the initial 30 min was seen in the obese when compared to lean subjects (24.0% vs 17.8% of the test meal; P=0.08). Weight loss was associated with a reduction in percentage gastric emptying during the initial 30 min (from 24.0% to 18.3% of the test-meal; P<0.02), whereas the overall 3 h emptying rate was unaffected (30.3% vs 30.9% per hour). Neither initial or overall emptying rate differed between reduced-obese and lean subjects.CONCLUSION: Overall 3 h gastric emptying rate was similar in obese and normal weight males, and unaffected by a major weight loss. However, percentage gastric emptying during the initial 30 min for a solid meal appeared to be increased in obese males and was normalized after a major weight reduction.

Low-fat diets and energy balance: how does the evidence stand in 2002?

The role of high-fat diets in weight gain and obesity is assessed by evidence-based principles. Four meta-analyses of weight change occurring on ad libitum low-fat diets in intervention trials consistently demonstrate a highly significant weight loss of 3-4 kg in normal-weight and overweight subjects (P < 0.001). The analyses also find a dose-response relationship, i.e. the reduction in percentage energy as fat is positively associated with weight loss. Weight loss is also positively related to initial weight; a 10 % reduction in dietary fat is predicted to produce a 4-5 kg weight loss in an individual with a BMI of 30 kg/m2. The non-fat macronutrient composition of the diet is also important. Whereas the glycaemic index of the carbohydrate may play a role for cardiovascular risk factors, there is so far no evidence that low-glycaemic index foods facilitate weight control. In contrast, intervention studies show that sugar in drinks is more likely to produce weight gain than solid sugar in foods. Although the evidence is weak, alcoholic beverages promote a positive energy balance, and wine may be more obesity-promoting than beer. Protein is more satiating and thermogenic than carbohydrates, and one intervention study has shown that an ad libitum low-fat diet where carbohydrate was replaced by protein produced more weight loss after 6 months (8.1 v. 5.9 kg). The evidence linking particular fatty acids to body fatness is weak. If anything, monounsaturated fat may be more fattening than polyunsaturated and saturated fats, and no ad libitum dietary intervention study has shown that a normal-fat high-monounsaturated fatty acid diet is equivalent or superior to a low-fat diet in the prevention of weight gain and obesity. The evidence strongly supports the low-fat diet as the optimal choice for the prevention of weight gain and obesity, while the use of a normal-fat high-monounsaturated fatty acid diet is unsubstantiated.

The association between the val/ala-55 polymorphism of the uncoupling protein 2 gene and exercise efficiency

BACKGROUND: Energy expenditure may partly be determined by genetic variations in uncoupling proteins. We have previously found an increased physical activity but a similar 24-h energy expenditure (EE) in subjects with the val/val-55 UCP2 genotype compared to those with the ala/ala genotype which indicates that the val-55 allele is statistically associated with a higher metabolic efficiency.DESIGN: EE during bicycling was determined by indirect calorimetry at three different loads (30, 40 and 60% of VO2max in eight subjects with the val/val-55 genotype (35±6 y weight=76.8±13.6 kg, VO2max=2.79±0.71 l/min) and eight subjects with the ala/ala-55 genotype (37±3 y, weight=78.3±16.5 kg, VO2max=2.66±0.41 l/min).RESULTS: Incremental exercise efficiency across the three different work levels was higher in the val/val (25.3%, c.i. 24.2–26.4%) than in the ala/ala (23.6%, c.i. 22.5–24.7%) genotype P<0.05. Gross exercise efficiency at 40% VO2max was higher in the val/val (15.3±0.6%) than in the ala/ala (13.5±0.4%) group.CONCLUSION: As the val/ala-55 polymorphism is located in a domain of the protein without any known function, the different exercise efficiency between the two genotypes most likely reflects a linkage disequilibrium with a functionally significant polymorphism in UCP2 or in the neighbouring UCP3 gene. The study suggests that variations in the UCP genes may affect not only basal metabolic rate but also influence energy costs of exercise.International Journal of Obesity (2001) 25, 467–471

Fat metabolism in formerly obese women

An impaired fat oxidation has been implicated to play a role in the etiology of obesity, but it is unclear to what extent impaired fat mobilization from adipose tissue or oxidation of fat is responsible. The present study aimed to examine fat mobilization from adipose tissue and whole body fat oxidation stimulated by exercise in seven formerly obese women (FO) and eight matched controls (C). Lipolysis in the periumbilical subcutaneous adipose tissue, whole body energy expenditure (EE), and substrate oxidation rates were measured before, during, and after a 60-min bicycle exercise bout of moderate intensity. Lipolysis was assessed by glycerol release using microdialysis and blood flow measurement by 133Xe clearance technique. The FO women had lower resting EE than C (3.77 +/- 1.01 vs. 4.88 +/- 0.74 kJ/min, P < 0.05) but responded similarly to exercise. Adipose tissue glycerol release was twice as high in FO than in C at rest (0.455 +/- 0.299 vs. 0.206 +/- 0.102 mumol.100 g-1.min-1, P < 0.05) but increased similarly in FO and C in response to exercise. Despite higher plasma nonesterified fatty acids (NEFA) in FO (P < 0.001), fat oxidation rates during rest and recovery were lower in FO than in C (1.32 +/- 0.84 vs. 3.70 +/- 0.57 kJ/min, P < 0.02) and fat oxidation for a given plasma NEFA concentration was lower at rest (P < 0.001) and during exercise (P = 0.01) in the formerly obese group. In conclusion, fat mobilization both at rest and during exercise is intact in FO, whereas fat oxidation is subnormal despite higher circulation NEFA levels. The lower resting EE and the failure to use fat as fuel contribute to a positive fat balance and weight gain in FO subjects.

The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women

Treatment with beta 2-agonists promotes fat loss and muscle growth in numerous species, but human studies are lacking. We studied the effect of a compound with beta 2-agonistic properties (ephedrine 20 mg/caffeine 200 mg [E + C]). Fourteen obese women were treated with a 4.2-MJ/d diet and either E + C or placebo (P) three times per day for 8 weeks in a double-blind study. Weight-loss was not different in the groups, but the E + C group lost 4.5 kg more body fat and 2.8 kg less fat-free mass (FFM). The decrease in 24-hour energy expenditure (EE) seen in the P group was 10% at day 1 and 13% at day 56, but was only 7% and 8% in the treated group (P = .044). The higher EE in the E +C group was entirely covered by fat oxidation. These findings provide evidence that promotion of fat loss and preservation of FFM during weight reduction may also be achieved pharmacologically in humans.

Lower-body fat mass as an independent marker of insulin sensitivity--the role of adiponectin.

AIMS:To study the association between lower-body fat and estimates of whole-body insulin sensitivity in middle-aged men with and without a history of juvenile onset obesity, and to determine the possible mediating role of fasting serum adiponectin level as an insulin-sensitizing peptide.METHODS:A total of 401 men aged 39–65 y, body mass index 18–54 kg/m2, participated in the study. The following variables were measured on the study participants: regional body fat distribution as assessed by dual energy X-ray absorptiometry, abdominal sagittal diameter, maximal oxygen uptake (VO2max), physical activity, fasting and post-glucose load levels of plasma glucose, serum insulin, and blood non-esterified fatty acid plus fasting levels of serum adiponectin and HbA1c.RESULTS:Lower-body fat mass was positively associated with insulin sensitivity as estimated by Matsudas index also after adjusting for age, lean tissue mass, trunkal fat mass, weight changes since draft board examination, VO2max and the level of physical activity. In a subgroup of men selected for a large lower-body fat mass, fasting serum insulin concentration was 24% lower (P<0.01) and fasting serum adiponectin 33% higher (P<0.005) compared to a subgroup of men with a small lower-body fat mass but with similar trunkal fat mass.CONCLUSION:Lower-body fat mass is positively associated with an estimate of insulin sensitivity independently of trunkal fat mass in both lean and obese middle-aged men and this effect could partly be statistically explained by variations in serum adiponectin levels.

The acute effect of D-tagatose on food intake in human subjects.

A double-blind randomized crossover study was performed with nineteen normal-weight men to investigate the effect on subsequent ad libitum food intake of replacing 29 g sucrose with 29 g D-tagatose as sweetener to a breakfast meal. D-Tagatose is a malabsorbed stereoisomer of fructose with potential application as a bulk sweetener. Food intake was measured at lunch offered 4 h after the breakfast meal, during the afternoon with access to abundant snacks, and finally at a supper buffet 9 h after the breakfast. Energy intake at lunch and during the snacking period was similar after ingesting the two sugars, while it was 15% lower after ingesting D-tagatose than with sucrose at supper (P < 0.05). Gastrointestinal factors such as the osmotic effects of unabsorbed D-tagatose causing distension of the gut might have mediated the acute appetite-suppressing effect. The present paper also refers to data from a preceding study in which we observed an increased self-reported energy intake after ingestion of D-tagatose compared with sucrose which, in fact, suggests a relative hyperphagic effect of D-tagatose. However, self-reported food intake may be biased by selective under-reporting and this subsequent study with a more controlled assessment of food intake was therefore conducted. This present study did not support any hyperphagic effect of D-tagatose, but rather suggests that D-tagatose may contribute to a reduced energy intake.

The effect of wine or beer versus a carbonated soft drink, served at a meal, on ad libitum energy intake.

BACKGROUND: Alcoholic beverage drinking may increase total energy intake at a meal by various mechanisms and this effect may depend on the sort of beverage.OBJECTIVE: To test the effect of wine, beer and a soft drink served with a normal meal on food and total energy intake in non-obese men.DESIGN: A supper meal consisting of three consecutive dishes was presented to 22 young men. Ad libitum energy intakes (EI) of the meal were measured at three different occasions in a cross-over design with red wine, lager beer or a carbonated soft drink. This was done in two studies with different design. In the first study the beverages were supplied ad libitum and in a second study the intake of the beverages was fixed: beer and soft drink at 9 ml/kg body weight and wine isoalcoholic to beer, 3.185 ml/kg body weight.RESULTS: In the ad libitum beverage study total EI was higher with wine than with the soft drink and beer (P<0.05). In the fixed beverage study differences in total EI did not reach statistical significance (P=0.14), although the intake of goulash was higher with wine and beer than with the soft drink (P<0.005).CONCLUSION: These data indicate that alcoholic beverages, and wine in particular, may enhance total EI at a meal relative to a soft drink, when served with no restriction.

Effects of the two β3-agonists, ZD7114 and ZD2079 on 24 hour energy expenditure and respiratory quotient in obese subjects

OBJECTIVE: To analyze the effect of two different β3-adrenoceptor agonists, ZD7114 and ZD2079 on 24 h energy expenditure (EE) and substrate oxidations in obese weight-stable subjects.DESIGN: Measurements of 24 h EE in a respiration chamber, before and after 14 days of treatment with one of the two β3-agonists or placebo during weight maintenance.SUBJECTS: ZD7114 study: 7 male and 15 female subjects, body mass index (BMI) 28–39 kg/m2, age 27–64 y; ZD2079 study: 10 male and 7 female subjects, BMI 27–39 kg/m2, age 31–60 y.MEASUREMENTS: EE was measured by indirect calorimetry, spontaneous physical activity (SPA) assessed by microwave radar, and 24 h heart rate was registered by telemetry. Serum potassium was measured to test for possible β2-adrenoceptor activity.RESULTS: No effects of ZD7114 were found on tested parameters whereas there was a trend for a stimulatory effect of ZD2079 on 24 h EE (day 14-pretreatment; ZD2079 vs placebo: 0.4±1.1 vs −2.0±0.4%, P=0.06) and on SPA (day 14-pretreatment; ZD2079 vs placebo: 3.4±4.5 vs −7.7±2.7%, P=0.05). However, average 24 h heart rate decreased from 77.5±3.2 to 73.8±2.6 min−1 from pre-treatment to day 14 with placebo but remained the same with ZD2079 (P=0.03). The latter suggests some β1-adrenoceptor activity of the compound.CONCLUSION: The lack of thermogenic response with ZD7114 and the very small and questionable response with ZD2079 probably demonstrate a lack of consistency between species in the responsiveness to β3-stimulation or a diversity in structure of the β3 receptor since both compounds have proven markedly selective thermogenic β3-properties in rodents.