The cause of obesity: are we barking up the wrong tree?
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Energy Metabolism↗
Biomedical subjects
Arne Astrup
Publications and source records attributed to Arne Astrup.
The effect of exercise and diet on glucose intolerance and substrate utilization?
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Blood Glucose↗
Increased 24-h energy expenditure in type 2 diabetes.
OBJECTIVE: The aim of this study was to determine whether overweight and obese individuals with type 2 diabetes have higher basal and 24-h energy expenditure compared with healthy control subjects before and after adjustment for body composition, spontaneous physical activity (SPA), sex, and age. RESEARCH DESIGN AND METHODS: Data from 31 subjects with type 2 diabetes and 61 nondiabetic control subjects were analyzed. The 24-h energy expenditure, basal metabolic rate (BMR), and sleeping energy expenditure (EEsleep) between 1:00 a.m. and 6:00 a.m. were measured in whole-body respiratory chambers. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: No significant differences in unadjusted EEsleep, BMR, and 24-h energy expenditure were observed between the type 2 diabetic group and the control group. After adjustment for fat-free mass (FFM), fat mass, SPA, sex, and age, EEsleep and BMR were, respectively, 7.7 and 6.9% higher in the type 2 diabetic group compared with the control group. This was equivalent to 144 +/- 40 kcal/day (P = 0.001) and 139 +/- 61 kcal/day (P = 0.026), respectively. Adjusted 24-h energy expenditure was 6.5% higher in the type 2 diabetic group compared with the nondiabetic control subjects (2,679 +/- 37 vs. 2,515 +/- 23 kcal/day, P = 0.002). In multiple regression analyses, FFM, fat mass, SPA, and diabetes status were all significant determinants of EEsleep and 24-h energy expenditure, explaining 83 and 81% of the variation, respectively. CONCLUSIONS: This study confirms reports in Pima Indians that basal and 24-h energy expenditure adjusted for body composition, SPA, sex, and age are higher in individuals with type 2 diabetes compared with nondiabetic control subjects and may be even more pronounced in Caucasians.
Absorptiometry, Photon↗
The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes.
OBJECTIVE: Glucagon-like peptide (GLP)-1 is a gut hormone that exerts incretin effects and suppresses food intake in humans, but its therapeutic use is limited due to its short half-life. This was a randomized, double-blind, parallel-group, placebo-controlled trial investigating the effect of the long-acting GLP-1 derivative liraglutide (NN2211) on glycemic control, body weight, body composition, and 24-h energy expenditure in obese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-three patients (mean +/- SD) aged 60.0 +/- 9.5 years, with HbA(1c) 7.5 +/- 1.2% and BMI 36.6 +/- 4.1 kg/m(2), were randomized to treatment with a single daily subcutaneous dose of 0.6 mg liraglutide (n = 21) or placebo (n = 12) for 8 weeks. In addition to weight and glycemic parameters, body composition was assessed by dual-energy X-ray absorptiometry (DEXA) scanning and 24-h energy expenditure in a respiratory chamber. RESULTS: After 8 weeks, liraglutide reduced fasting serum glucose (liraglutide, -1.90 mmol/l, and placebo, 0.27 mmol/l; P = 0.002) and HbA(1c) (liraglutide, -0.33%, and placebo, 0.47%; P = 0.028) compared with placebo. No change in body weight was detected (liraglutide, -0.7 kg, and placebo, -0.9 kg; P = 0.756). There was a nonsignificant trend toward a decrease in total fat mass (liraglutide, -0.98%, and placebo, -0.12%; P = 0.088) and toward an increase in lean body mass (liraglutide, 1.02%, and placebo, 0.23%; P = 0.118) in the liraglutide group compared with the placebo group. Twenty-four-hour energy expenditure was unaffected by the treatment (liraglutide, -12.6 kJ/h, and placebo, -13.7 kJ/h; P = 0.799). CONCLUSIONS: Eight weeks of 0.6-mg liraglutide treatment significantly improved glycemic control without increasing weight in subjects with type 2 diabetes compared with those on placebo. No influence on 24-h energy expenditure was detected.
Blood Glucose↗
Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies.
Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro. CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term (<6 months) trials in humans find little evidence to support that CLA reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However, there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy. CLA also decreases the fat content of both human and bovine milk. In conclusion, although CLA appears to attenuate increases in body weight and body fat in several animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in humans and may actually have adverse effects on human health.
Animals↗
Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans.
Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-alpha). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [mean body mass index (BMI): 39.7 kg/m2, n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m2, n = 19) compared with lean men (mean BMI: 23.4 kg/m2, n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL-8, and TNF-alpha on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% (P < 0.05) increase in plasma adiponectin and a 45% (P < 0.05) increase in adipose tissue mRNA levels; 2) plasma adiponectin was 53% (P < 0.01) higher in lean compared with obese men, and plasma adiponectin was inversely correlated with adiposity, insulin sensitivity, and IL-6; and 3) TNF-alpha (P < 0.01) and IL-6 plus its soluble receptor (P < 0.05) decreased adiponectin mRNA levels in vitro. The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. This could be of importance for the association between cytokines (e.g., IL-6) and insulin resistance and atherosclerosis.
Adiponectin↗
Effects of different dietary fat types on postprandial appetite and energy expenditure.
OBJECTIVE: Observational studies suggest that monounsaturated (MUFA) and trans fatty acids (TRANS) are more fattening than polyunsaturated fatty acids (PUFA). Therefore, the aim of this study was to investigate the acute effect of intake of PUFA, MUFA, or TRANS on appetite and energy expenditure (EE). RESEARCH METHODS AND PROCEDURES: Three test meals were randomly given in a cross-over design to 19 overweight (BMI: 26.8 +/- 0.4 kg/m2), young (25.2 +/- 0.7 years) men. The fat-rich breakfasts (0.8 g fat/kg body weight, 60% energy from fat) varied only in the source of C:18-fat. EE was measured continuously in a respiration chamber, and appetite sensations were rated by visual analog scales before and every 30 minutes, for 5 hours, after the meal. After 5 hours, an ad libitum meal was served, and energy intake was registered. Sensory evaluations of all meals were given using visual analog scales. Data were analyzed by two-way ANOVA. RESULTS: There were no differences in basal or postprandial values of appetite ratings and EE, in subsequent ad libitum energy intake, or in the sensory evaluation of the test meals among the 3 test days. DISCUSSION: Giving acutely large amounts of MUFA, PUFA, or TRANS did not impose any differences in appetite and EE in overweight humans. However, studies with extended protocols and other subject groups are warranted to investigate the long-term effect of dietary fat quality on the regulation of energy balance and body weight.
Adult↗
Weight loss and increased mortality: epidemiologists blinded by observations?
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Epidemiologic Studies↗
Meals with similar energy densities but rich in protein, fat, carbohydrate, or alcohol have different effects on energy expenditure and substrate metabolism but not on appetite and energy intake.
BACKGROUND: It has been suggested that the satiating power of the 4 macronutrients follows the oxidation hierarchy: alcohol > protein > carbohydrate > fat. However, the experimental evidence for this is still scarce. OBJECTIVE: The goal was to investigate the effects on appetite, energy intake and expenditure, and substrate metabolism of meals rich in 1 of the 4 macronutrients. DESIGN: Subjective appetite sensations, ad libitum food intake, energy expenditure, substrate metabolism, and hormone concentrations were measured for 5 h after breakfast meals with similar energy density and fiber contents but rich in either protein (32% of energy), carbohydrate (65% of energy), fat (65% of energy), or alcohol (23% of energy). Subjects were normal-weight, healthy women (n = 9) and men (n = 10) studied in a crossover design. RESULTS: There were no significant differences in hunger or satiety sensations or in ad libitum energy intake after the 4 meals. Diet-induced thermogenesis was larger after the alcohol meal (by 27%; P < 0.01), whereas protein produced an intermediary response (17%; NS) compared with carbohydrate and fat (meal effect: P < 0.01). After the alcohol meal, fat oxidation and leptin concentrations were greatly suppressed (meal effects, P < 0.0001 and P < 0.05) and triacylglycerol concentrations were as high as after the fat meal. CONCLUSION: Intake of an alcohol-rich meal stimulates energy expenditure but suppresses fat oxidation and leptin more than do isoenergetically dense meals rich in protein, carbohydrate, or fat. Despite differences in substrate metabolism and hormone concentrations, satiety and ad libitum energy intake were not significantly different between meals. Our data, therefore, do not support the proposed relation between the macronutrient oxidation hierarchy and the satiety hierarchy.
Adult↗
Effect of chewing gum containing nicotine and caffeine on energy expenditure and substrate utilization in men.
BACKGROUND: Nicotine replacement therapy limits weight gain after smoking cessation. This finding is partly attributable to the thermogenic effect of nicotine, which may be enhanced by caffeine. OBJECTIVE: We assessed the acute thermogenic effects of chewing gum containing different doses of nicotine and caffeine. DESIGN: This randomized, double-blind, placebo-controlled, crossover study included 12 healthy, normal-weight men (aged 18-45 y). Energy expenditure was measured with indirect calorimetry before and 2.5 h after subjects chewed each of 7 different types of gum containing the following doses of nicotine/caffeine: 0/0, 1/0, 2/0, 1/50, 2/50, 1/100, and 2/100 mg/mg. RESULTS: The thermogenic responses (increases over the response to placebo) were 3.7%, 4.9%, 7.9%, 6.3%, 8.5%, and 9.8%, respectively, for the gums containing 1/0, 2/0, 1/50, 2/50, 1/100, and 2/100 mg nicotine/mg caffeine (P < 0.05 for all). Adding caffeine to 1 and 2 mg nicotine significantly enhanced the thermogenic response, but changing the caffeine dose (from 50 to 100 mg) did not change the thermogenic effect. None of the combinations changed the respiratory quotient compared with placebo, which indicates that glucose and fat oxidation rates were increased to a similar extent. Side effects occurred only with 2 mg nicotine. CONCLUSIONS: One milligram of nicotine has a pronounced thermogenic effect, which can be increased by approximately 100% by adding 100 mg caffeine. Increasing the nicotine dose to 2 mg does not increase the thermogenic effect but produces side effects in most subjects. Caffeine may be useful in preventing weight gain after smoking cessation if its thermogenic effect can be used to enhance nicotine's effect on long-term energy balance.
Adult↗
Leptin and bone mineral density: a cross-sectional study in obese and nonobese men.
Leptin has been suggested to decrease bone mineral density (BMD). This observational analysis explored the relationship between serum leptin and BMD in 327 nonobese men (controls) (body mass index 26.1 +/- 3.7 kg/m(2), age 49.9 +/- 6.0 yr) and 285 juvenile obese men (body mass index 35.9 +/- 5.9 kg/m(2), age 47.5 +/- 5.1 yr). Whole-body dual-energy x-ray absorptiometry scan measured BMD, fat mass, and lean mass. Fasting serum leptin (nanograms per milliliter) was strongly associated with fat mass (kilograms) in both controls (r = 0.876; P < 0.01) and juvenile obese (r = 0.838; P < 0.001). An inverse relation between BMD adjusted for body weight and serum leptin emerged in both the control group (r = -0.186; P < 0.01) and the juvenile obese group (r = -0.135; P < 0.05). In a multiple linear regression, fat mass, lean body mass, and occupational physical activity were positively associated with BMD in the control group, whereas in the juvenile obese, only lean body mass was positively associated with BMD and smoking negatively associated with BMD. Our study supports that leptin is inversely associated with BMD and may play a direct role in the bone metabolism in nonobese and obese Danish males, but it also stresses the fact that the strong covariation between the examined variables is a shortcoming of the cross-sectional design.
Adult↗
Abnormal sympathoadrenal activity, but normal energy expenditure in hypopituitarism.
In this study of 23 hypopituitary patients and 26 healthy controls, we have addressed whether the obese state of substituted hypopituitary patients is facilitated by abnormal sympathoadrenal activity or energy expenditure (EE). All patients received adequate substitution therapy including GH therapy. The investigation program included assessment of sympathoadrenal activity (urinary catecholamines), body composition (dual-energy x-ray absorptiometry), appetite sensations (visual analog scale), and EE (indirect calorimetry in respiration chamber). Twenty-four-hour urinary epinephrine adjusted for lean body mass and fat mass was significantly lower in patients compared with controls. GH and hydrocortisone were single negative predictors of urinary epinephrine. The major determinants of EE in patients were lean body mass and fat mass, explaining 96, 95, and 80% of the variance in 24-h EE, sleeping EE, and basal metabolic rate, respectively. Addition of urinary catecholamines explained another 1-4% of the variance in 24-h EE and basal metabolic rate, respectively. Lean patients exhibited significantly more hunger than obese patients and lean controls. In conclusion, hypopituitary patients have lower sympathoadrenal activity but normal EE, compared with healthy controls. This may reflect a central defect in hypopituitarism, however the possible impact of long-term GH and hydrocortisone treatment requires further attention.
Adrenal Glands↗
Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men.
OBJECTIVE: To study the association between anthropometric and metabolic parameters as well as the effect of weight loss on plasma levels of the adipose tissue-derived cytokines interleukin-8 (IL-8), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in abdominal obese men. SUBJECTS: Nineteen obese (mean body mass index (BMI): 38.6+/-0.6 kg/m(2)) and ten lean men (mean BMI: 23.4+/-0.4 kg/m(2)) were included in the study. The obese subjects received a 4.2 MJ/day diet for 8 weeks, followed by 8 weeks on energy restriction (6.2 MJ/day) and 8 weeks on a weight-maintenance diet. MEASUREMENTS: A dual energy X-ray absorptiometry (DEXA)-scan was performed to estimate body composition. Plasma levels of IL-8, IL-6 and TNF-alpha were measured by a specific ELISA method. Insulin sensitivity was assessed by the homeostasis model assessment method (HOMA). RESULTS: Plasma levels of IL-8 and IL-6 were 30-40% higher in obese as compared with lean subjects (P<0.05), whereas no group difference in TNF-alpha was observed. During the intervention, obese subjects obtained a 30% reduction in fat mass (P<0.001), fasting insulin (P<0.05) and HOMA (P<0.05). Plasma levels of TNF-alpha and IL-6 were decreased by 25-30% (P<0.001) but IL-8 was increased by 30% (P<0.001) after weight loss. IL-8 and IL-6 were correlated with measures of insulin resistance, and changes in IL-6 but not IL-8 were correlated with the improvement in insulin sensitivity after weight loss. CONCLUSION: Plasma levels of IL-8 and IL-6 were found to be increased and were correlated with measures of insulin resistance in abdominal obese male subjects. Weight loss was associated with changes in the circulating levels of IL-8, IL-6 and TNF-alpha indicating that these cytokines are influenced by weight loss.
Adult↗
[The CARMEN trial: increased intake of carbohydrates--simple or complex--and unchanged blood lipids in overweight subjects].
INTRODUCTION: The purpose was to investigate the long-term effect of ad libitum low-fat, high-carbohydrate diets with mainly simple or complex carbohydrates on body weight and blood lipids. MATERIAL AND METHODS: A six-months controlled randomised multicentre trial with the participation of five European centres. A total of 398 moderately obese subjects (BMI: 30.4 +/- 2.7 kg/m2, mean +/- SD) were randomised to four groups: Control diet group with normal macronutrient intake, a low-fat/high simple carbohydrate group, a low-fat/high complex carbohydrate group and a seasonal control group. RESULTS: After six months we found a drop in body weight of 1.7 kg (p < 0.05) in the simple and of 2.6 kg (p < 0.001) in the complex carbohydrate group compared with the control diet group. Fat mass decreased by 1.9 kg (p < 0.05) and 2.4 kg (p < 0.001) in the simple and complex carbohydrate group, respectively, compared with the control diet group. There were no significant changes or group differences in fasting blood lipids, glucose, insulin, or leptin. DISCUSSION: The results show that it is favourable to replace dietary fat by carbohydrates (simple or complex) in relation to body weight regulation. No detrimental effects were seen on blood lipids in contrast to previous contentions. Our results underline the importance of a low-fat/high-carbohydrate diet in the management of obesity and the ensuing health problems.
Adult↗
Fat mass measured by DXA varies with scan velocity.
OBJECTIVE: To study the influence of scan velocities of DXA on the measured size of fat mass, lean body mass, bone mineral content and density, and total body weight. RESEARCH METHODS AND PROCEDURES: The subjects were 71 healthy white adults, 38 women and 33 men. The mean age was 41.7 +/- 13.5 years and body mass index was 28.6 +/- 5.6 kg/m(2). The subjects were scanned consecutively in slow, medium, and fast scan mode by a Lunar DPX-IQ DXA scanner. RESULTS: Throughout the body mass index and sagittal height ranges, scanned lean body mass significantly decreased with higher scan velocity and lean body mass was 2.7% lower in fast than in medium mode (p < 0.0001). In contrast, fat mass, percentage of body fat, and bone mineral contents were higher with increasing scan velocity. Areas not analyzed by the scanner, so called blue spots, increased with scan velocity and sagittal height, and their presence significantly enhanced the error. Body weight estimated by DXA in slow mode was -0.8% lower than scale weight in the women (p < 0.001) and -0.2% in men (not significant), and the difference was greater with increasing scan velocity. DISCUSSION: Scan velocity significantly influences the measured fat mass size, lean body mass, bone mineral content, and body weight. To obtain the most accurate results, slow mode is preferable and fast scans should be avoided. Future studies should report and take scan velocity into consideration.
Absorptiometry, Photon↗
An observational study of slimming behavior in Denmark in 1992 and 1998.
OBJECTIVE: To elucidate how frequent weight-loss attempts are made, the methods used to achieve weight loss, and the extent to which the outcome is positive. RESEARCH METHODS AND PROCEDURES: Two independent interviews were conducted in 1992 and in 1998, each with 1200 randomly selected adult subjects. Each survey was designed to ensure an equal distribution of age, gender, and geographical regions in Denmark. RESULTS: The proportion of subjects having attempted weight loss did not change from 1992 to 1998, although the prevalence of overweight and obesity increased from 1992 (overweight, 30%; obesity, 6%) to 1998 (overweight, 35%; obesity, 8%). Almost twice as many women (61%) than men (32%) had attempted weight loss (p < 0.0001). Slimming occurred more often in subjects <50 years (51%) than >50 years (39%) (p < 0.0001), although overweight and obesity were more frequent in the elderly. Over-the-counter diet pills or meal replacements were associated with a negative outcome of slimming treatment (p < 0.0001). DISCUSSION: Approximately half of all adult Danes have attempted weight loss, particularly women and individuals <50 years. This finding is inconsistent with the fact that overweight and obesity are more prevalent in men and in individuals >50 years. Changes in habitual diet and increased physical activity are the most prevalent modes of slimming, whereas the use of over-the-counter diet pills or meal replacements has decreased from 1992 to 1998. This development may have a positive impact on future body- weight-management strategies.
Adult↗
Effect of protein intake on bone mineralization during weight loss: a 6-month trial.
OBJECTIVE: The long-term effect of dietary protein on bone mineralization is not well understood. RESEARCH METHODS AND PROCEDURES: Sixty-five overweight (body mass index, 25 to 29.9 kg/m(2)) or obese (> or =30 kg/m(2)) subjects were enrolled in a randomized, placebo-controlled, 6-month dietary-intervention study comparing two controlled ad libitum diets with matched fat contents: high protein (HP) or low protein (LP). Body composition was assessed by DXA. RESULTS: In the HP group, dietary-protein intake increased from 91.4 g/d to a 6-month intervention mean of 107.8 g/d (p < 0.05) and decreased in the LP group from 91.1 g/d to 70.4 g/d (p < 0.05). Total weight loss after 6 months was 8.9 kg in the HP group, 5.1 kg in the LP group, and none in the control group. After 6 months, bone mineral content (BMC) had declined by 111 +/- 13 g (4%) in the HP group and by 85 +/- 13 g (3%) in the LP group (not significant). Loss of BMC was more positively correlated with loss of body fat mass (r = 0.83; p < 0.0001) than with loss of body weight. Six-month BMC loss, adjusted for differences in fat loss, was greater in the LP group than in the HP group [difference in LP vs. HP, 44.8 g (95% confidence interval, 16 to 73.8 g); p < 0.05]. Independent of change in body weight and composition during the intervention, highprotein intake was associated with a diminished loss of BMC (p < 0.01). DISCUSSION: Body-fat loss was the major determinant of loss of BMC, and we found no adverse effects of 6 months of high-protein intake on BMC.
Absorptiometry, Photon↗
Dietary fat is a major player in obesity--but not the only one.
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Cardiovascular Diseases↗