Common variants near melanocortin receptor 4 (MC4R) have been related to fatness and type 2 diabetes. We examined the associations of rs17782313 and rs17700633 in relation to body fat, body fat distribution, metabolic traits, weight development and energy expenditure.
Obese young men (n = 753, BMI > or = 31.0 kg m(-2)) and a randomly selected group (n = 874) identified from a population of 174 800 men were re-examined in three surveys at mean ages 35, 46 and 49 years (S-35, S-46 and S-49). Measurements were available at upto eight times from birth to adulthood. Logistic regression analysis was used to assess odds ratio (OR) for the presence of the carrier allele for a given difference in phenotypic values.
Rs17782313 minor C-allele was associated with overall, abdominal and peripheral fatness (range of OR = 1.06-1.14 per z-score units) at all three surveys, although only consistently significant at S-35 and S-46. Rs17700633 minor A-allele was also associated with the fatness measures, but significantly so only at S-49 for overall and abdominal fatness (range of OR = 1.03-1.15 per z-score units), and peripheral fatness (OR = 1.15-1.20 per z-score units). There were only few significant associations with metabolic traits. The rs17782313 C-allele and the rs17700633 A-allele were both associated with lower high-density lipoprotein cholesterol (range of OR = 0.64-0.84 per mol l(-1)), significantly at S-46. The rs17700633 A-allele was significantly associated with insulin (OR = 1.25 per 50 pmol l(-1)), leptin (OR = 1.42 per 10 ng microl(-1)) and insulin sensitivity (OR = 0.81 per model unit). The rs17782313 C-allele and the rs17700633 A-allele were both associated with BMI in childhood and adolescence (range of OR = 1.04-1.17 per z-score units), significant for the rs17782313 C-allele at the age of 13-19 years and for rs17700633 A-allele at age 7, 10, 13 and 19 years. No significant associations were found for energy expenditure.
Near MC4R variants appear to contribute to body fat, body fat distribution, some metabolic traits, weight development during childhood, but not to energy expenditure.
BACKGROUND: Studies of long-term intake of industrially produced trans fatty acids (TFA) and n-3 polyunsaturated fatty acids (PUFA) suggest opposite effects on cardiovascular disease risk. Common mechanisms of action are probable. OBJECTIVE: To examine the effects on cardiovascular risk markers of dietary enrichment with TFA or n-3 PUFA. DESIGN: Randomized, double-blind, parallel intervention trial. SETTING: Department of Human Nutrition, The Royal Veterinary and Agricultural University. SUBJECTS: In all, 87 healthy males included, 79 completed. INTERVENTION: Subjects were randomly assigned to 8 weeks of a daily intake of 33 g of experimental fats from either partially hydrogenated soy oil containing 20 g of TFA, 12 g of fish oil with approximately 4 g of n-3 PUFA and 21 g of control fat, or 33 g of control fat. The experimental fats were incorporated into bakery products. Plasma lipids, blood pressure, heart rate variability (HRV), arterial dilatory capacity, compliance, and distensibility were recorded before and after intervention and at follow-up 12 weeks after the intervention. RESULTS: High-density lipoprotein cholesterol (HDL-C) decreased in the TFA group and triglycerides and mean arterial blood pressure decreased in the n-3 PUFA group compared to the control group. HRV, arterial dilatory capacity, compliance, and distensibility were unchanged. CONCLUSION: The results indicate that the association between coronary heart disease risk and intake of TFA and n-3 PUFA relates only modestly to changes in traditional risk markers. SPONSORSHIP: Danish Medical Research Council (Grant no. 22-01-0390), Center of Advanced Food Research (Copenhagen, Denmark) (Grant no. KVL-R-2001-107), the Danish Heart Association (Grant no. 99-2-3-45-22748), Novozymes (Bagsvaerd, Denmark), Aarhus Olie (Aarhus, Denmark), and from private sources. The experimental fats were provided by Pronova Biocare (Aalesund, Norway) and Aarhus Olie (Aarhus, Denmark).
OBJECTIVES: To compare importance of rate of initial weight loss for long term outcome in obese patients and to compare efficacy of two different weight maintenance programmes. DESIGN: Subjects were randomised to either rapid or slow initial weight loss. Completing patients were re-randomised to one year weight maintenance programme of ad lib diet or fixed energy intake diet. Patients were followed up one year later. SETTING: University research department in Copenhagen, Denmark. SUBJECTS: 43 (41 women) obese adults (body mass index 27-40) who were otherwise healthy living in or around Copenhagen. INTERVENTIONS: 8 weeks of low energy diet (2 MJ/day) or 17 weeks of conventional diet (5 MJ/day), both supported by an anorectic compound (ephedrine 20 mg and caffeine 200 mg thrice daily); one year weight maintenance programme of ad lib, low fat, high carbohydrate diet or fixed energy intake diet ( 5 kg at follow up. RESULTS: Mean initial weight loss was 12.6 kg (95% confidence interval 10.9 to 14.3 kg) in rapid weight loss group and 12.6 (9.9 to 15.3) kg in conventional diet group. Rate of initial weight loss had no effect on weight maintenance after 6 or 12 months of weight maintenance or at follow up. After weight maintenance programme, the ad lib group had maintained 13.2 (8.1 to 18.3) kg of the initial weight loss of 13.5 (11.4 to 15.5) kg, and the fixed energy intake group had maintained 9.7 (6.1 to 13.3) kg of the initial 13.8 (11.8 to 15.7) kg weight loss (group difference 3.5 (-2.4 to 9.3) kg). Regained weight at follow up was greater in fixed energy intake group than in ad lib group (11.3 (7.1 to 15.5) kg v 5.4 (2.3 to 8.6) kg, group difference 5.9 (0.7 to 11.1) kg, P 5 kg (P
The present study assessed the possible familial effect in 71 healthy Caucasian siblings on each of the variables determining the inter-individual variations in energy expenditure (EE) measured under standardized conditions. We found that the 24-h EE measured in respiration chambers of 71 siblings from 32 different families was positively correlated with fat-free mass, which explained 82% of the variation between subjects (P