Allelic Variants of Melanocortin 3 Receptor Gene (MC3R) and Weight Loss in Obesity: A Randomised Trial of Hypo-Energetic High- versus Low-Fat Diets

INTRODUCTION: The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets. SUBJECTS AND METHODS: This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat) diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes. RESULTS: No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04) and dominant models (p = 0.03). These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103-rs1543873 (p = 0.06), rs6014646-rs6024730 (p = 0.05) and rs3746619-rs3827103 (p = 0.10) displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes. CONCLUSION: The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss after a 10-week dietary intervention with hypo-energetic diets in obese Europeans

Soluble urokinase plasminogen activator receptor as a marker for use of antidepressants.

OBJECTIVES: Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants. METHODS: suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register. RESULTS: For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1st to the 4th quartile (HR = 1.72, 95% CI: 1.11-2.69). For women, it increased by 108% from the 1st to the 4th quartile (HR = 2.08, 95% CI: 1.45-2.98). Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002). CONCLUSIONS: High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression

Effect¹ of previous use of antidepressants on log2-transformed suPAR.

1<p>Estimates are from linear regressions adjusting for age (continuous).</p><p>Effect^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110555#nt102" target="_blank">1</a>} of previous use of antidepressants on log2-transformed suPAR.</p

Risk of an incident hospital diagnosis of depression according to the suPAR level.

<p>Risk of an incident hospital diagnosis of depression according to the suPAR level.</p

Kaplan-Meier plot with antidepressants as outcome and the suPAR level quartiles as explanatory variables (n = 9305).

<p>The 4^th quartile is the highest values. Log-rank test: p<0.0001.</p

Soluble urokinase plasminogen activator receptor (suPAR) (ng/ml) in blood donors according to sex and age.

<p>Soluble urokinase plasminogen activator receptor (suPAR) (ng/ml) in blood donors according to sex and age.</p

Clinical correlates of weight loss and attrition during a 10-week dietary intervention study:Results from the NUGENOB project

Objective: The aim of this study was to identify the pre-treatment subject characteristics and weight loss changes as determinants of weight loss and attrition during a 10-week dietary intervention study. Methods: A total of 771 obese subjects (BMI 35.6 kg/m(2)) of both genders were included from 8 clinical centres in 7 European countries, who underwent a 10-week dietary intervention study comparing two hypo-energetic (-600 kcal/day) diets varying in fat content. Results: The multiple regression model showed that weight loss at week 10 was predicted by: 6.55 + 1.27 x early weight loss (kg) at week 1 + 1.35 x gender (R(2) = 0.28, p /= 4 kg weight loss at week 5 emerged as an optimal predictor for reaching at least 10% weight loss at week 10. Greater attrition likelihood was predicted by high-fat diet, decreased early and half-way weight losses. Conclusion: Early and half-way weight losses are associated with and could contribute to prediction of the final weight loss and attrition. Copyright (c) 2012 S. Karger GmbH, Freiburg