A Astrup

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 30u2005min for 180u2005min after, ingestion of a 2.5u2005MJ solid test meal. Gastric emptying was estimated scintigraphically. An ad libitum lunch was served 3u2005h after the test meal.SUBJECTS: Nineteen non-diabetic obese (body mass index (BMI) 34.1–43.8u2005kg/m2) and 12 lean (BMI 20.4–24.7u2005kg/m2) males. All obese subjects were re-examined after a mean stabilised weight loss of 18.8u2005kg (95% CI 14.4–23.2).RESULTS: Total area under the GLP-1 response curve (AUCtotal,u2005GLP-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,u2005GIP and AUCincremental,u2005GIP were lowered (P<0.05). An inverse correlation was observed between AUCincremental,u2005GIP 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 short-term high dietary calcium intake on 24-h energy expenditure, fat oxidation, and fecal fat excretion

BACKGROUND:Observational studies have shown an inverse association between dietary calcium intake and body weight, and a causal relation is likely. However, the underlying mechanisms are not understood.OBJECTIVE:We examined whether high and low calcium intakes from mainly low-fat dairy products, in diets high or normal in protein content, have effects on 24-h energy expenditure (EE) and substrate oxidation, fecal energy and fat excretion, and concentrations of substrates and hormones involved in energy metabolism and appetite.DESIGN:In all, 10 subjects participated in a randomized crossover study of three isocaloric 1-week diets with: low calcium and normal protein (LC/NP: 500 mg calcium, 15% of energy (E%) from protein), high calcium and normal protein (HC/NP: 1800 mg calcium, 15E% protein), and high calcium and high protein (HC/HP: 1800 mg calcium, 23E% protein).RESULTS:The calcium intake had no effect on 24-h EE or fat oxidation, but fecal fat excretion increased ∼2.5-fold during the HC/NP diet compared with the LC/NP and the HC/HP diets (14.2 vs 6.0 and 5.9 g/day; P<0.05). The HC/NP diet also increased fecal energy excretion as compared with the LC/NP and the HC/HP diets (1045 vs 684 and 668 kJ/day; P<0.05). There were no effects on blood cholesterol, free fatty acids, triacylglycerol, insulin, leptin, or thyroid hormones.CONCLUSIONS:A short-term increase in dietary calcium intake, together with a normal protein intake, increased fecal fat and energy excretion by ∼350 kJ/day. This observation may contribute to explain why a high-calcium diet produces weight loss, and it suggests that an interaction with dietary protein level may be important.

The effect of caffeine, green tea and tyrosine on thermogenesis and energy intake

Objectives:To investigate the effect of three different food ingredients tyrosine, green tea extract (GTE) and caffeine on resting metabolic rate and haemodynamics, and on ad libitum energy intake (EI) and appetite.Methods:Twelve healthy, normal weight men (age: 23.7±2.6 years, mean±s.d.) participated in a four-way crossover, randomized, placebo-controlled, double-blind study. Treatments were administered as tablets of 500u2009mg GTE, 400u2009mg tyrosine, 50u2009mg caffeine, or placebo, and were separated by >3-day washout. The acute thermogenic response was measured in a ventilated hood system for 4u2009h following ingestion. Blood pressure, heart rate (HR), and subjective appetite sensations were assessed hourly and ad libitum EI 4u2009h post-dose.Results:Caffeine induced a thermogenic response of 6% above baseline value (72±25u2009kJ per 4u2009h, mean±s.e.) compared to placebo (P<0.0001). The thermogenic responses to GTE and tyrosine were not significantly different from placebo. Tyrosine tended to increase 4-h respiratory quotient by 1% compared to placebo (0.01±0.005, P=0.05). Ad libitum EI was not significantly different between treatments but was reduced by 8% (−403±183u2009kJ), 8% (−400±335u2009kJ) and 3% (−151±377u2009kJ) compared to placebo after intake of tyrosine, GTE and caffeine, respectively. No significant difference in haemodynamics was observed between treatments.Conclusions:Only caffeine was thermogenic in the given dose and caused no haemodynamic side effects. The sample size was probably too small to detect any appetite suppressant properties of the treatments. Further investigations are required.

Effects of soy supplementation on blood lipids and arterial function in hypercholesterolaemic subjects.

Background:Studies on soy supplementation suggest a cardioprotective potential.Objective:To examine the effects on LDL cholesterol and arterial function as a result of dietary enrichment with soy supplementation.Design:A Randomized, double blind, parallel intervention trial.Setting:Department of Endocrinology and Metabolism C, Aarhus University Hospital, and Department of Human Nutrition, The Royal Veterinary and Agricultural University, Denmark.Subjects:In all, 100 hypercholesterolaemic but otherwise healthy subjects were included in the study of which 89 completed it.Interventions:Subjects were randomly assigned to 24 weeks of daily intake of either a soy supplement, Abalon® (30u2009g soy protein, 9u2009g cotyledon fibre and 100u2009mg isoflavones) or placebo (30u2009g of casein). The soy supplement and placebo were provided in two sachets daily that were stirred in water. Fasting plasma lipids, TNF-α, homocysteine, insulin sensitivity, homeostasis model assessment (HOMA-IR), serum insulin, serum glucose, blood pressure as well as Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and plasma lipids to a fat-rich meal were recorded before and after the intervention. In a sub study in 32 subjects, arterial dilatory capacity, compliance, and distensibility were recorded before and after the intervention.Results:In the main study, no difference in fasting plasma lipid levels or insulin sensitivity was found between soy-based supplement and placebo. A significant postprandial increase in GIP to the meal test was observed in the soy group (P<0.05). In a substudy, no difference between the groups in changes in flow-mediated vasodilatation (P=0.84) was detected, while the soy supplementation caused a reduction in LDL and total cholesterol.Conclusions:No significant effects on blood lipids were observed in the main study to a soy supplementation in hypercholesterolaemic subjects after 24 weeks. In the substudy, the soy supplementation, however, reduced LDL and total cholesterol but did not influence markers of arterial function.Sponsorship:Nutri Pharma ASA, Oslo, Norway.

Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial

Background/Objectives:Observational studies indicate that sugar-sweetened soft drinks (SSSD) may promote obesity, among other factors, owing to low-satiating effects. The effect of energy in drinks on appetite is still unclear. We examined the effect of two isocaloric, but macronutrient, different beverages (SSSD versus semi-skimmed milk) and two non-energy-containing beverages (aspartame-sweetened soft drink (ASSD) and water) on appetite, appetite-regulating hormones and energy intake (EI).Subjects/Methods:In all, 24 obese individuals were included in a crossover trial. Each subject was served either 500u2009ml of SSSD (regular cola: 900u2009kJ), semi-skimmed milk (950u2009kJ), ASSD (diet cola: 7.5u2009kJ), or water. Subjective appetite scores, ghrelin, GLP-1, and GIP concentrations were measured at baseline and continuously 4-h post intake. Ad libitum EI was measured 4u2009h after intake of the test drinks.Results:Milk induced greater subjective fullness and less hunger than regular cola (P<0.05). Also, milk led to 31% higher GLP-1 (95% CI: 20, 44; P<0.01) and 45% higher GIP (95% CI: 23, 72; P<0.01) concentrations compared with SSSD. Ghrelin was equally 20% lower after milk and SSSD compared with water. The total EI (ad libitum EI+EI from the drink) was higher after the energy-containing drinks compared with diet cola and water (P<0.01).Conclusions:Milk increased appetite scores and GLP-1 and GIP responses compared with SSSD. The energy containing beverages were not compensated by decreased EI at the following meal, emphasizing the risk of generating a positive energy balance by consuming energy containing beverages. Furthermore, there were no indications of ASSD increased appetite or EI compared with water.

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 39–65u2009y, body mass index 18–54u2009kg/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.

Effects of different fractions of whey protein on postprandial lipid and hormone responses in type 2 diabetes

Background/Objectives:Exacerbated postprandial lipid responses are associated with an increased cardiovascular risk. Dietary proteins influence postprandial lipemia differently, and whey protein has a preferential lipid-lowering effect. We compared the effects of different whey protein fractions on postprandial lipid and hormone responses added to a high-fat meal in type 2 diabetic subjects.Subjects/Methods:A total of 12 type 2 diabetic subjects ingested four isocaloric test meals in randomized order. The test meals contained 100u2009g of butter and 45u2009g of carbohydrate in combination with 45u2009g of whey isolate (iso-meal), whey hydrolysate (hydro-meal), α-lactalbumin enhanced whey (lac-meal) or caseinoglycomacropeptide enhanced whey (CGMP-meal). Plasma concentrations of triglyceride, retinyl palmitate, free fatty acid, insulin, glucose, glucagon, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide were measured before and at regular intervals until 8-h postprandially.Results:We found no statistical significant differences between meals on our primary variable triglyceride. The retinyl palmitate response was higher after the hydro-meal than after the iso- and lac-meal in the chylomicron-rich fraction (P=0.008) while no significant differences were found in the chylomicron-poor fraction. The hydro- and iso-meal produced a higher insulin response compared with the lac- and CGMP-meal (P<0.001). Otherwise no significant differences in the hormone responses were found in the incremental area under the curve over the 480-min period.Conclusions:A supplement of four different whey protein fractions to a fat-rich meal had similar effects on postprandial triglyceride responses in type 2 diabetic subjects. Whey isolate and whey hydrolysate caused a higher insulin response.

Effect of diet-induced energy deficit and body fat reduction on high-sensitive CRP and other inflammatory markers in obese subjects

Aims:To dissociate the possible differential effects of negative energy balance and reduction in body fat mass (FM) on inflammatory markers: C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), haptoglobin, transferrin and the adipokines leptin and adiponectin.Methods:Thirty-three obese subjects (BMI: 34.0±3.1u2009kg/m2, age: 43.0±10.5 years, mean±s.d., 16 men) participated in a 20-week controlled dietary intervention divided into four periods. Weight reduction was induced by an 8-week low energy diet (3.4u2009MJu2009d−1) (LED-1) followed by a 4-week weight maintenance program (M-1). Subsequently participants underwent an additional 4-week LED (4.2u2009MJu2009d−1) (LED-2) followed by a final 4-week weight maintenance diet (M-2). Blood samples and anthropometrics were assessed at baseline and after LED-1, M-1, LED-2 and M-2.Results:Body weight was significantly reduced by 13% (13.7±4.0u2009kg, P<0.0001) after LED-1. However, a reduction in high-sensitive CRP (hs-CRP) by 35% (−1.1 (95% CI: −2.5:0.2) mgu2009l−1, P=0.02) only became apparent after LED-2, which produced an additional weight loss of 2.9u2009kg compared to baseline, and it was maintained after M-2 (−1.0 (−1.4:0.4) mgu2009l−1, P=0.02). Also IL-6 was reduced by 21% (−0.6 (−2.4:0.2) ngu2009l−1, P=0.02) after M-2. The reductions in hs-CRP and IL-6 were both associated with reduction in FM but not body weight. Haptoglobin, transferrin and leptin were significantly reduced after both LED-1 and LED-2, but increased during weight maintenance. Adiponectin was not significantly changed during the intervention.Conclusions:The results suggest that, whereas haptoglobin and transferrin respond more rapidly and are more susceptible to the acute change in energy balance, a reduction in hs-CRP and IL-6 seems to be achieved by a reduction in FM when a new steady state has been established.

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 9u2005ml/kg body weight and wine isoalcoholic to beer, 3.185u2005ml/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 24u2005h energy expenditure (EE) and substrate oxidations in obese weight-stable subjects.DESIGN: Measurements of 24u2005h 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) 28–39u2005kg/m2, age 27–64u2005y; ZD2079 study: 10 male and 7 female subjects, BMI 27–39u2005kg/m2, age 31–60u2005y.MEASUREMENTS: EE was measured by indirect calorimetry, spontaneous physical activity (SPA) assessed by microwave radar, and 24u2005h 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 24u2005h 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 24u2005h heart rate decreased from 77.5±3.2 to 73.8±2.6u2005min−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.