The effect of weight loss on whole-body and tissue-specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy.

OBJECTIVE: This study (1) investigated the effect of weight loss on whole-body and tissue-specific insulin sensitivity and on intrahepatic lipid (IHL) content and composition and (2) investigated the association between weight-loss-induced changes in insulin sensitivity and IHL content in individuals with overweight or obesity. METHODS: In this secondary analysis of the European SWEET project, 50 adults (age 18-65 years) with overweight or obesity (BMI ≥ 25 kg/m2 ) followed a low-energy diet (LED) for 2 months. At baseline and after the LED, body composition (dual-energy x-ray absorptiometry), IHL content and composition (proton magnetic resonance spectroscopy), whole-body insulin sensitivity (Matsuda index), muscle insulin sensitivity index (MISI), and hepatic insulin resistance index (HIRI) were determined (7-point oral glucose tolerance test). RESULTS: The LED reduced body weight (p < 0.001). This was accompanied by increased Matsuda index and reduced HIRI (both p < 0.001) but no change in MISI (p = 0.260). Weight loss decreased IHL content (mean [SEM], 3.9% [0.7%] vs. 1.6% [0.5%], p < 0.001) and the hepatic saturated fatty acid fraction (41.0% [1.5%] vs. 36.6% [1.9%], p = 0.039). The reduced IHL content was associated with an improvement in HIRI (r = 0.402, p = 0.025). CONCLUSIONS: Weight loss decreased IHL content and the hepatic saturated fatty acid fraction. The decrease in IHL content was associated with weight-loss-induced improvement in hepatic insulin sensitivity in individuals with overweight or obesity.

Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber.

BACKGROUND: The mechanism of protein-induced satiety remains unclear. OBJECTIVE: The objective was to investigate 24-h satiety and related hormones and energy and substrate metabolism during a high-protein (HP) diet in a respiration chamber. DESIGN: Twelve healthy women aged 18-40 y were fed in energy balance an adequate-protein (AP: 10%, 60%, and 30% of energy from protein, carbohydrate, and fat, respectively) or an HP (30%, 40%, and 30% of energy from protein, carbohydrate, and fat, respectively) diet in a randomized crossover design. Substrate oxidation, 24-h energy expenditure (EE), appetite profile, and ghrelin and glucagon-like peptide 1 (GLP-1) concentrations were measured. RESULTS: Sleeping metabolic rate (6.40 +/- 0.47 compared with 6.12 +/- 0.40 MJ/d; P < 0.05), diet-induced thermogenesis (0.91 +/- 0.25 compared with 0.69 +/- 0.24 MJ/d; P < 0.05), and satiety were significantly higher, and activity-induced EE (1.68 +/- 0.32 compared with 1.86 +/- 0.41; P < 0.05), respiratory quotient (0.84 +/- 0.02 compared with 0.88 +/- 0.03; P < 0.0005), and hunger were significantly lower during the HP diet. There was a tendency for a greater 24-h EE during the HP diet (P = 0.05). Although energy intake was not significantly different between the diet groups, the subjects were in energy balance during the HP diet and in positive energy balance during the AP diet. Satiety was related to 24-h protein intake (r2 = 0.49, P < 0.05) only during the HP diet. Ghrelin concentrations were not significantly different between diets. GLP-1 concentrations after dinner were higher during the HP than during the AP diet (P < 0.05). CONCLUSION: An HP diet, compared with an AP diet, fed at energy balance for 4 d increased 24-h satiety, thermogenesis, sleeping metabolic rate, protein balance, and fat oxidation. Satiety was related to protein intake, and incidentally to ghrelin and GLP-1 concentrations, only during the HP diet.

Activity-induced GLP-1 release in lean and obese subjects.

The aim of the study was to determine whether physical activity stimulates GLP-1 release on the short-term in normal weight and in obese subjects compared to rest and, furthermore, whether modest weight loss affects GLP-1 release or sensitivity in the obese. Normal weight (n=28; 12 males, 16 females; BMI 22.9+/-1.4; age 35+/-12.7), as well as obese subjects (n=27; 21 males, 6 females; BMI 30.9+/-2.7; age 47.1+/-11.86) were tested in a resting and a physical activity condition. Obese subjects were matched over two groups for a weight loss period of 3 months. After weight loss, the tests were repeated. The area under the curve (AUC pmol/lxmin) for GLP-1 concentrations was significantly increased in the physical activity condition compared to rest in lean subjects (P=0.05) as well as in the obese subjects after weight loss (P<0.05), but not in the obese subjects before weight loss. Physical activity-stimulated GLP-1 release in lean and obese subjects after a weight loss period supports the idea of a neuroendocrine loop in addition to distal-intestinal stimulation of GLP-1 release. Modest weight loss might be effective for increasing GLP-1 sensitivity to acute stimulation.

Sex differences in HPA axis activity in response to a meal.

BACKGROUND: Sex may influence the relationship between HPA axis functioning and obesity. This has been suggested to be due to sex-specific differences in body composition, body fat distribution and psychological variables. Age and the use of oral contraceptives may also influence the relationship between HPA axis functioning and obesity. OBJECTIVE: To systematically investigate whether body composition, body fat distribution, psychological variables, age, or possible oral contraceptive use contribute to sex differences in HPA axis activity in response to a meal. METHODS: Subjects were men (n=19) and women (n=19) between 18 and 51 years old with BMI between 20.3 and 33.2 kg/m(2). HPA axis activity was measured by salivary free cortisol levels before consuming a meal, and at 45, 75 and 125 min postprandial on four repeated test days. Anthropometric and body composition measurements were performed. Questionnaires were used to assess cognitive eating behavior and trait anxiety level. RESULTS: No differences between the test days in postprandial cortisol responses appeared. Responses were significantly higher in men compared with women (p<.05). No significant correlations were found between cortisol concentrations and sex-specific body composition or body fat distribution. Psychological variables did not contribute to differences in cortisol responses after a meal between men and women. In women, baseline cortisol concentrations correlated inversely with age (p=.024). CONCLUSION: Higher HPA axis activity following a meal in men vs. women remained irrespective of sex-specific differences in body composition, body fat distribution, psychological variables, or in age. In women baseline cortisol concentrations were age-dependent.

Nutrient-stimulated glucagon-like peptide 1 release after body-weight loss and weight maintenance in human subjects.

Glucagon-like peptide 1 (GLP-1) is a peptide hormone that is released in response to nutrient ingestion. Postprandial GLP-1 release has been reported to be attenuated in obese subjects, but reports on the effect of weight loss on GLP-1 are conflicting. The aim of the present study was to clarify the effect of a weight-loss period and a consecutive weight-maintenance period on nutrient-stimulated GLP-1 release in obese subjects. Nutrient-stimulated (standard breakfast; 1.9 MJ) GLP-1 release was investigated in thirty-two obese subjects on three occasions: before weight loss (T1) (BMI 30.0 (sd 2.5) kg/m(2)); after a 6-week very-low-energy diet (VLED) (T2) (BMI 27.6 (sd 2.3) kg/m(2)); after a 3-month weight-maintenance period (T3) (BMI 27.9 (sd 2.3) kg/m(2)). At each occasion, following a fasting blood sample the test meal was fed and blood was drawn every 30 min for 2 h relative to ingestion in order to determine plasma GLP-1, insulin, glucose and NEFA concentrations. Subjects lost 7 (sd 3.4) kg during the VLED (P<0.0001) and regained 1 (sd 3.2) kg during the weight-maintenance period (NS). The area under the curve for nutrient-stimulated plasma GLP-1 (pmol/l x h) was significantly decreased (P=0.01) at T2 (6.8 (sd 1)) compared with T1 (12.8 (sd 2.9)) and T3 (11.1 (sd 1.5)). Since we found a rebound of concentrations after a weight-maintenance period, decrease after weight loss seems to be transient and possibly due to a negative energy balance.

Glucagon-like peptide-1 release and satiety after a nutrient challenge in normal-weight and obese subjects.

The present study was conducted to assess whether glucagon-like peptide-1 (GLP-1) release and appetite after a breakfast with or without an additional galactose/guar gum stimulation is different in normal-weight compared with overweight/obese subjects. Twenty-eight overweight/obese (BMI 30.3 (sd 2.7) kg/m2; age 44.3 (sd 9.7) years) and thirty normal-weight subjects (BMI 22.8 (sd 1.4), age 31.5 (sd12.8) years) participated in a crossover study. Fasting and postprandial plasma GLP-1, insulin, glucose and free fatty acid concentrations were measured in response to either a galactose (50 g)/guar gum (2.5 g) load (836 kJ) and a standard breakfast (1.9 MJ; GG), or water (250 ml) and the standard breakfast (W) every 30 min relative to the ingestion for 120 min. Appetite was assessed using 100 mm visual analogue scales. GLP-1 concentrations were significantly increased after GG at 30 and 60 min compared with W in both groups. Plasma GLP-1 concentrations in the W condition were higher in normal-weight than overweight/obese subjects (P=0.03). No difference was observed in the GG condition between groups. Satiety was increased in normal-weight compared with overweight/obese subjects in the GG condition at 30 (P=0.02) and 60 (P=0.04) min. We conclude that after a standard breakfast with water, GLP-1 release was lower in the overweight/obese than the normal-weight subjects. However, postprandial GLP-1 release in overweight/obese subjects was no different from that of normal-weight subjects when galactose/guar gum was added to the breakfast. The latter was not mirrored by subjective feelings of satiety. Disturbed perception of the physiological feedback of a satiety hormone rather than disturbed feedback itself might contribute to obesity.

Decreased glucagon-like peptide 1 release after weight loss in overweight/obese subjects.

OBJECTIVE: Postprandial glucagon-like peptide 1 (GLP-1) release seems to be attenuated in obese subjects. Results on whether weight loss improves GLP-1 release are contradictory. The aim of this study was to further investigate the effect of weight loss on basal and postprandial GLP-1 release in overweight/obese subjects. RESEARCH METHODS AND PROCEDURES: Thirty-two overweight/obese subjects participated in a repeated measurement design before (BMI, 30.3 +/- 2.8 kg/m2; waist circumference, 92.6 +/- 7.8 cm; hip circumference, 111.1 +/- 7.4 cm) and after a weight loss period of 6 weeks (BMI, 28.2 +/- 2.7 kg/m2; waist circumference, 85.5 +/- 8.5 cm; hip circumference, 102.1 +/- 9.2 cm). During weight loss, subjects received a very-low-calorie diet (Optifast) to replace three meals per day. Subjects came to the laboratory fasted, and after a baseline blood sample, received a standard breakfast (1.9 MJ). Postprandially, blood samples were taken every one-half hour relative to intake for 120 minutes to determine GLP-1, insulin, glucose, and free fatty acids from plasma. Appetite ratings were obtained with visual analog scales. RESULTS: After weight loss, postprandial GLP-1 concentrations at 30 and 60 minutes were significantly lower than before weight loss (p < 0.05). Glucose concentrations were also lower, and free fatty acids were higher compared with before weight loss. Ratings of satiety were increased, and hunger scores were decreased after weight loss (p < 0.05). DISCUSSION: In overweight/obese subjects, GLP-1 concentrations after weight loss were decreased compared with before weight loss, and nutrient-related stimulation was abolished. This might be a response to a proceeding negative energy balance. Satiety and GLP-1 seem to be unrelated in the long term.