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Biomedical subjects

Arne Astrup

Publications and source records attributed to Arne Astrup.

At least 19 recordsLinked to original sources
PubMed2005

Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men.

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups. The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P < 0.05) and an increase in fat oxidation by 29% (P < 0.05). However, a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast (0.84 +/- 0.1 to 0.79 +/- 0.1, P < 0.05). Furthermore, lean body mass (LBM) was increased by GH-adm. only [62.8 +/- 2.5 kg (baseline) vs. 64.7 +/- 2.4 kg (after), P < 0.001]. In conclusion, GH-adm. increases 24-h EE, which may be partly explained by increased LBM. Furthermore, GH-adm. stimulates fat combustion, especially in the postabsorptive state.

Adult↗
PubMed2005

Mutation analysis of the preproghrelin gene: no association with obesity and type 2 diabetes.

OBJECTIVE: To investigate the preproghrelin gene for variants and their association with obesity and type 2 diabetes. DESIGN AND METHOD: 82 obese probands were analyzed for mutations using single-strand conformational polymorphism, heteroduplex analyses and sequencing. Association studies were performed in 234 juvenile-onset obese and 323 lean men and in 557 type 2 diabetic and 233 glucose tolerant subjects. RESULTS: We identified two novel variants, 36C > T and IVS3 + 715delC, and 4 known variants, Arg51Gln, Leu72Met, Gln90Leu, and IVS1 + 169G > A. None of the variants showed any significant association with obesity or type 2 diabetes or estimates of glucose and lipid metabolism in glucose tolerant subjects. CONCLUSION: Variation in the preproghrelin gene is not associated with juvenile-onset obesity, type 2 diabetes or related phenotypes among the examined Danish Caucasian subjects.

Adolescent↗
PubMed2005

Novel variants in the putative peroxisome proliferator-activated receptor {gamma} promoter and relationships with obesity in men.

Yet unidentified variants within the peroxisome proliferator-activated receptor gamma (PPARgamma) 2 promoter may explain the inconsistent reports on associations between variants in the coding region and obesity or diabetes. Thus, we examined the putative PPARgamma2 promoter (-3371 to +43 bp) for variants in 83 subjects with obesity or type 2 diabetes. We identified eight variants, seven of which were novel, including -792A>G, -816C>T, -882T>C, -1505G>A, -1881C>T, -1884T>A, -2604T>C, and -2953A>G. The variants -816C>T, -1505G>A, -1881C>T, and -2604T>C were in total linkage disequilibrium, and there was a high degree of linkage disequilibrium between several of the novel variants and Pro12Ala. The novel variants were, together with Pro12Ala and 1431C>T, examined for relationships with obesity among 234 men with early-onset obesity with a BMI at age approximately 20 years of 33.2+/-2.5 kg/m2 and 323 nonobese men with a BMI of 21.7+/-2.5 kg/m2, who were also reexamined after approximately 29 years. The prevalence of the identified variants was not significantly different between the two groups, and the variants did not affect changes in BMI over time. In conclusion, the identified novel variants in the PPARgamma2 promoter region do not explain the reported discrepancies in the association of previously identified variants with obesity and type 2 diabetes.

Body Mass Index↗
PubMed2005

The N363S polymorphism of the glucocorticoid receptor and metabolic syndrome factors in men.

OBJECTIVE: To test the associations between the N363S polymorphism of the glucocorticoid receptor gene (NR3C1) and factors related to the metabolic syndrome in middle-aged men with and without juvenile-onset obesity. RESEARCH METHODS AND PROCEDURES: This study included two groups of middle-aged men, who were originally identified at 20 years of age at the draft boards. One group (n = 208; age, 48 +/- 6 years) was selected on the basis of juvenile-onset obesity (BMI > or = 31 kg/m(2)). The other group consisted of mainly nonobese men randomly sampled from the same population in parallel with the obese men (n = 299; age, 50 +/- 7 years). The subjects were genotyped for the N363S polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Body composition was measured by DXA. Glucose metabolism was evaluated by an oral glucose tolerance test, and the Matsudas index was calculated as a proxy for insulin sensitivity. Serum triglycerides and total and high-density lipoprotein-cholesterol were measured in the fasting state. RESULTS: Among the men with juvenile-onset obesity, carriers (n = 17) of the 363S allele had a lower whole body fat percentage, after accounting for differences in BMI and higher Matsudas index, compared with the noncarriers. The difference in Matsudas index lost statistical significance after the difference in body fat was accounted for. In the randomly sampled men, these variables did not relate to genotype. No relationship between carriers and noncarriers was found in body fat distribution or serum lipids. DISCUSSION: This study suggests that, in men developing obesity early in life, the 363S allele is associated with less adiposity at a given BMI, leading to higher insulin sensitivity.

Absorptiometry, Photon↗
PubMed2005

Change in beta1-adrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss.

The aim of the present study was to examine gene expression and protein concentrations of beta(1)- and beta(2)-adrenergic receptors in subcutaneous adipose tissue in obese subjects in response to weight loss. Eighteen obese subjects were studied during diet-induced weight loss. Beta-adrenergic receptor mRNA levels were quantified by reverse transcription-PCR-HPLC. Beta-adrenergic receptor protein concentrations were measured by Western blotting using fluorescence laser scanning for detection. Subjects lost 12.8+/-0.8 kg (mean+/-S.E.M.) during diet treatment. There was a 34% decrease in the beta(1)-adrenergic receptor mRNA level (0.92+/-0.09 compared with 0.61+/-0.06 amol/microg of DNA; P<0.002). Beta(2)-adrenergic receptor mRNA did not decrease significantly. Beta(2)-adrenergic receptor protein concentration decreased 37% (25.5+/-7.1 compared with 16.0+/-5.6 arbitrary units/ng of DNA; P=0.008), whereas beta(1)-adrenergic receptor protein concentration did not decrease significantly. The degree of weight loss was correlated with the concentration of beta(1)-adrenergic receptor protein (r=0.65, P<0.003) and changes in receptor protein concentration (r=0.50, P=0.035) during the very-low-calorie diet. In conclusion, the present study demonstrates a relationship between beta(1)-adrenergic receptor protein concentration in adipose tissue and the degree of weight loss. This relationship is not directly related to energy expenditure and deserves further investigation.

Adipose Tissue↗
PubMed2005

The role of dietary fat in obesity.

Current scientific evidence indicates that dietary fat plays a role in weight loss and maintenance. Meta-analyses of intervention trials find that fat-reduced diets cause a 3-4-kg larger weight loss than normal-fat diets. A 10% reduction in dietary fat can cause a 4-5-kg weight loss in individuals with initial body mass index of 30 kg m (-2). Short-term trials show that nonfat dietary components are equally important. Sugar-sweetened beverages promote weight gain, and replacement of energy from fat by sugar-sweetened beverages is counterproductive in diets aimed at weight loss. Protein has been shown to be more satiating than carbohydrate, and fat-reduced diets with a high protein content (20-25% of energy) may increase weight loss significantly. There is little evidence that low-glycemic index foods facilitate weight control. Evidence linking certain fatty acids to body fatness is weak. Monounsaturated fatty acids may even be more fattening than polyunsaturated and saturated fats. No ad libitum dietary intervention study has shown that a normal-fat, high-monounsaturated fatty acid diet is comparable to a low-fat diet in preventing weight gain. Current evidence indicates that the best diet for prevention of weight gain, obesity, type 2 diabetes, and cardiovascular disease is low in fat and sugar-rich beverages and high in carbohydrates, fiber, grains, and protein.

Body Mass Index↗
PubMed2005

Effect of sucrose on inflammatory markers in overweight humans.

BACKGROUND: Observational studies have found that dietary glycemic load is positively associated with C-reactive protein (CRP) concentrations in healthy humans, which suggests that the type of carbohydrate ingested influences inflammatory activity. OBJECTIVE: We investigated the effect of a diet with a high content of sucrose or artificial sweeteners on the inflammatory markers CRP, haptoglobin, and transferrin in overweight subjects. DESIGN: Overweight men and women consumed daily food and drink supplements containing either sucrose [n = 21; body mass index (BMI, in kg/m2): 28.0] or artificial sweeteners (n = 20; BMI: 27.6), predominantly from soft drinks (70%; average approximately 1.3 L/d) for 10 wk. RESULTS: During the intervention, sucrose intake increased by 151% in the sucrose group and decreased by 42% in the sweetener group, resulting in a 1.6-kg weight gain in the sucrose group and a 1.2-kg weight loss in the sweetener group over 10 wk (P < 0.001). Concentrations of haptoglobin, transferrin, and CRP increased by 13%, 5%, and 6%, respectively, in the sucrose group and decreased by 16%, 2%, and 26%, respectively, in the sweetener group (between-group differences: P = 0.006, P = 0.01, and P = 0.1, respectively). Adjustment for changes in body weight and energy intake did not substantially influence this outcome. CONCLUSIONS: The study shows that in the present group of overweight subjects a high consumption of sugar-sweetened foods and drinks increased haptoglobin and transferrin but had, at best, only a limited influence on CRP.

Adult↗
PubMed2005

Mutation analysis of the MCHR1 gene in human obesity.

OBJECTIVE: The importance of the melanin-concentrating hormone (MCH) system for regulation of energy homeostasis and body weight has been demonstrated in rodents. We analysed the human MCH receptor 1 gene (MCHR1) with respect to human obesity. DESIGN: This consisted of genomic screening of 13.4 kb encompassing the MCHR1 in extremely obese German children and adolescents and association analyses for two coding single nucleotide polymorphisms (SNPs). To confirm initial positive association results, additional association studies and transmission disequilibrium tests in further German, Danish, French and American samples were conducted. Selected SNPs were investigated using functional in vitro studies and reporter gene assays. METHODS: Single-stranded conformation polymorphism analysis, re-sequencing, PCR-restriction fragment length polymorphism analyses, tetra-primer amplification refractory mutation systems, matrix-assisted laser desorption/ionization time of flight mass spectrometry and reporter gene assays were carried out as well as measuring inositol phosphate formation, inhibition of cAMP formation and activation of p42/44 MAP kinase. RESULTS: We identified 11 infrequent variations and two SNPs in the MCHR1 coding sequence and 18 SNPs (eight novel) in the flanking sequence. Association and transmission disequilibrium with obesity were detected for several SNPs in independent study groups of German obese children and adolescents and controls. In two German samples, encompassing 4056 and 295 individuals, trends towards association with obesity were detected. Findings in a second epidemiological German sample and in Danish, French and American samples were negative. Functional in vitro studies as well as reporter gene assays revealed no significant results. CONCLUSION: Our initial association of MCHR1 alleles/haplotype detected might be related to juvenile-onset obesity, conditional on a particular genetic and/or environmental background. Alternatively, we could not exclude the possibility that the initially detected association represented a false positive finding.

Adolescent↗
PubMed2004

Food intake is inhibited by oral oleoylethanolamide.

Oleoylethanolamide (OEA) may be an endogenous regulator of food intake, and intraperitoneal injection of this compound decreases food intake in 24 h-starved rats. It is generally believed that this kind of lipid amide is rapidly catabolized in the gastrointestinal tract, thereby preventing its use as an oral antiobesity compound. We now show that oral OEA inhibits food intake dose dependently at 90 min after food presentation to starved rats. Food intake was reduced by 15.5% (P < 0.01) by administration of 10 mg/kg OEA. [(3)H]OEA was used to assess the degree of catabolism in the gastrointestinal tract. The endogenous level of this acylethanolamide was increased 11 times in the intestinal tissue (to 3.91 +/- 0.98 nmol/g tissue, mean +/- SEM) at 90 min after food presentation, based on the finding of 0.48% of the dose as intact OEA. These findings reveal unexpected properties of orally administered OEA, which may have potential as a cheap and safe antiobesity drug.

Administration, Oral↗
PubMed2004

Major increase in prevalence of overweight and obesity between 1987 and 2001 among Danish adults.

OBJECTIVE: The aim of the study was to examine the secular trends in the prevalence of obesity (BMI >or= 30.0 kg/m(2)) and overweight (25.0 <or= BMI < 30.0 kg/m(2)) in Danish adults between 1987 and 2001. RESEARCH METHODS AND PROCEDURES: The study included self-reported weight and height of 10,094 men and 9897 women 16 to 98 years old, collected in a series of seven independent cross-sectional surveys. Prevalence and changes in prevalence of obesity and overweight stratified by sex and age groups were determined. RESULTS: The prevalence of obesity more than doubled between 1987 and 2001, in men from 5.6% to 11.8% [odds ratio (OR) = 2.3, 95% confidence interval (CI) = 1.9 to 2.8, p < 0.0001] and in women from 5.4% to 12.5% (OR = 2.6, 95% CI = 2.1 to 3.2, p < 0.0001), with the largest increase among the 16- to 29-year-old subjects (men, from 0.8% to 7.5%, OR = 10.2, 95% CI = 4.1 to 25.3, p < 0.0001; women, from 1.4% to 9.0% OR = 7.0, 95% CI = 3.5 to 14.1, p < 0.0001). Between 1987 and 2001, the prevalence of overweight increased from 34% to 40% in men and from 17% to 27% in women. DISCUSSION: The prevalence of overweight and obesity in Denmark has increased substantially between 1987 and 2001, particularly among young adults, a development that resembles that of other countries. There is clearly a need for early preventive efforts in childhood to limit the number of obesity-related complications in young adults.

Adolescent↗
PubMed2004

Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects.

OBJECTIVE: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low-calorie diet. RESEARCH METHODS AND PROCEDURES: Obese subjects (30 < or = BMI < 50 kg/m(2)) 18 to 75 years old received a low-calorie diet for 8 weeks. Those who lost > or =8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. RESULTS: Of the 701 subjects enrolled, 80% lost > or =8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run-in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. DISCUSSION: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low-calorie diet-and produced additional clinically significant weight loss beyond that achieved by a low-calorie diet.

Adolescent↗