Mechanical efficiency: associations with body composition and glycemic profile in healthy adults.

The aim of this study was to assess the association between net mechanical efficiency (NME) and body composition and glycemic profile, in middle-aged (38.3 ± 14.3 years) participants from the Quebec Family Study (QFS). Analyses were completed on a sample of 605 participants (271 males and 334 females) who performed a submaximal exercise test on an ergometer consisting of three consecutive 6-min workloads at increasing intensity during which respiratory gas exchange was assessed. The calculation of NME [power output/ (vO2-vO2seated before exercise)] was based on the values of the last 3 min of the first workload at a targeted power output of 30 W. Correlations between NME and dependent variables were computed separately in males and females. Associations between NME and body composition and glucose-insulin variables were assessed by comparing groups of subjects categorized in sex-specific tertiles of NME after adjustments for age. Significant negative correlations were observed between NME and body composition and glycemic profile in both sexes. Comparison across tertiles showed that individuals with high NME displayed more favorable adiposity and glycemic profiles. These differences remained significant after further adjustments for participation in vigorous physical activity, cardiorespiratory fitness, and mean exercise respiratory exchange ratio whereas most differences in glucose-insulin variables became non-significant after further adjustment for percent body fat. QFS familial data indicate that the heritability of NME reaches about 30%. In conclusion, the results of this study show that beyond aerobic fitness and physical activity-participation, mechanical efficiency is an additional activity-related variable that is independently associated with variations in body composition and glycemic profile.

Effects of sodium intake and cardiorespiratory fitness on body composition and genetic susceptibility to obesity: results from the Quebec Family Study.

The main aim of this study was to evaluate the effects of Na intake and cardiorespiratory fitness (CRF) on body composition. The study was also intended to assess whether Na intake and/or CRF mediate the genetic susceptibility to obesity. Analyses were performed on a sample of 526 adult participants from the Quebec Family Study for whom a complete data set was available for nutrient and energy intake, CRF and body composition variables. The effects of Na, CRF and their interaction were analysed by comparing sex-specific tertiles using general linear mixed models. In both males and females, we observed a significant effect of Na intake and CRF on all body composition variables. However, in females only, we found that the effect of Na intake on body composition variables varies according to CRF level such that high Na intake was associated with increased body fatness, but only in females with low CRF. This interaction effect remained significant after statistical adjustment for total sugar, fat and energy intake. Using mediation analysis, we also found Na intake and CRF to be significant mediators of the relationship between a polygenic risk score of obesity based on > 500 000 genetic variants and BMI or waist circumference. In conclusion, the current study shows that Na intake influences body composition via mechanisms that interact with aerobic fitness, especially in females. Furthermore, both Na intake and CRF seem to be involved in the expression of the genetic susceptibility to obesity.

Relationship between lifestyle habits and cardiovascular risk factors in familial hypercholesterolemia.

BACKGROUND AND AIM: Little is known about the cardioprotective potential of a healthy lifestyle in familial hypercholesterolemia (FH). The objective of this study was to evaluate the relationship between lifestyle and cardiovascular risk factors in adults with FH. METHODS AND RESULTS: This cross-sectional study leveraged data from the CARTaGENE Quebec population-based cohort (Canada). Participants with FH were identified using the validated Simplified Canadian Definition for FH. A healthy lifestyle score (HLS), ranging from 0 to 5, was calculated per adherence to 5 lifestyle habits: 1) not smoking; 2) being physically active (≥150 min/week of moderate or vigorous physical activity); 3) eating a healthy diet (Alternate Healthy Eating Index ≥50%); 4) having a light to moderate alcohol consumption (men: 1-30 g/day; women: 1-15 g/day); and 5) sleeping 7-8 h/day. Among the 122 included individuals (women, n = 78; men, n = 44; mean age ± SD: 57.3 ± 6.7 years), 92 (75.4%) had a HLS ≤3/5, while only 5 (4.1%) had a HLS of 5/5. After adjustments for sex, age, body mass index, and lipid-lowering medication use, we found no evidence of an association between the HLS and concentrations of LDL-cholesterol (ß = 0.04, 95% CI = -0.08, 0.15 mmol/L; P = 0.54). However, the HLS was favorably associated with HbA1c levels (ß = -0.07, 95% CI = -0.13, -0.01%; P = 0.02), and statistical trends suggested favorable associations with HDL-cholesterol (ß = 0.06, 95% CI = -0.02, 0.14 mmol/L; P = 0.06) and waist circumference (ß = -2.22, 95% CI = -4.62, 0.17 cm; P = 0.07). CONCLUSION: This study suggests that a healthy lifestyle is favorably associated with CVD risk factors in adults with FH.

Dietary Mediators of the Genetic Susceptibility to Obesity-Results from the Quebec Family Study.

BACKGROUND: Recent studies showed that eating behaviors such as disinhibition, emotional and external eating, and snacking mediate genetic susceptibility to obesity. It remains unknown if diet quality and intake of specific food groups also mediate the genetic susceptibility to obesity. OBJECTIVE: This study aimed to assess if diet quality and intakes of specific food groups mediate the association between a polygenic risk score (PRS) for BMI and BMI and waist circumference (WC). We hypothesized that poor diet quality, high intakes of energy-dense food groups, and low intakes of nutrient-dense food groups mediate the genetic susceptibility to obesity. METHODS: This cross-sectional study included 750 participants (56.3% women, aged 41.5 ± 14.9 y, BMI 27.8 ± 7.5 kg/m2) from the Quebec Family Study. A PRSBMI based on >500,000 genetic variants was calculated using LDpred2. Dietary intakes were assessed with a 3-d food record from which a diet quality score (i.e. Nutrient Rich Food Index 6.3) and food groups were derived. Mediation analyses were conducted using a regression-based and bootstrapping approach. RESULTS: The PRSBMI explained 25.7% and 19.8% of the variance in BMI and WC, respectively. The association between PRSBMI and BMI was partly mediated by poor diet quality (ß = 0.33 ± 0.12; 95% CI: 0.13, 0.60), high intakes of fat and high-fat foods (ß = 0.46 ± 0.16; 95% CI: 0.19, 0.79) and sugar-sweetened beverages (ß = 0.25 ± 0.14; 95% CI: 0.05, 0.60), and low intakes of vegetables (ß = 0.15 ± 0.08; 95% CI: 0.03, 0.32), fruits (ß = 0.37 ± 0.12; 95% CI: 0.17, 0.64), and dairy products (ß = 0.17 ± 0.09; 95% CI: 0.02, 0.37). The same trends were observed for WC. CONCLUSIONS: The genetic susceptibility to obesity was partly mediated by poor diet quality and intakes of specific food groups. These results suggest that improvement in diet quality may reduce obesity risk among individuals with high genetic susceptibility and emphasize the need to intervene on diet quality among these individuals.

Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium.

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10-6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

Circulating glutamate level as a potential biomarker for abdominal obesity and metabolic risk.

BACKGROUND AND AIM: Circulating level of glutamate, a by-product of the catabolism of branched-chain amino acids, has been positively correlated with visceral adipose tissue accumulation and waist circumference (WC). The aim of the present study was to assess the potential of using glutamate level to identify individuals with abdominal obesity and a high cardiometabolic risk. METHODS AND RESULTS: The study sample included 99 men and 99 women. Fasting serum glutamate was measured using the Biocrates p180 kit. Anthropometric and metabolic variables were used to identify individuals with abdominal obesity (WC ≥ 95 cm in both sexes), the hypertriglyceridemic waist (HTW) phenotype and the metabolic syndrome (MetS). Mean (±SD) age was 34.1 ± 10.1 years, mean BMI was 29.0 ± 6.2 kg/m2 and mean WC was 92.7 ± 16.5 cm. Glutamate was strongly correlated with WC (r = 0.66 for men; r = 0.76 for women, both p < 0.0001) and multiple markers of metabolic dysfunction, particularly fasting triglyceride level (r = 0.59 for men; r = 0.57 for women, both p < 0.0001), HDL-cholesterol level (r = -0.45, p < 0.0001 in both sexes) and the HOMA-IR index (r = 0.65 for men; r = 0.60 for women, both p < 0.0001). Logistic regressions showed that glutamate had an excellent accuracy to identify individuals with abdominal obesity (ROC_AUC: 0.90 for both sexes), a good accuracy to identify those with the HTW phenotype (ROC_AUC: 0.82 for men; 0.85 for women) and fair-to-good accuracy for the MetS (ROC_AUC: 0.78 for men; 0.89 for women). CONCLUSION: Glutamate level may represent an interesting potential biomarker of abdominal obesity and metabolic risk.

Familial resemblances in human whole blood transcriptome.

BACKGROUND: Considering the implication of gene expression in the susceptibility of chronic diseases and the familial clustering of chronic diseases, the study of familial resemblances in gene expression levels is then highly relevant. Few studies have considered the contribution of both genetic and common environmental effects to familial resemblances in whole blood gene expression levels. The objective is to quantify the contribution of genetic and common environmental effects in the familial resemblances of whole blood genome-wide gene expression levels. We also make comparisons with familial resemblances in blood leukocytes genome-wide DNA methylation levels in the same cohort in order to further investigate biological mechanisms. RESULTS: Maximal heritability, genetic heritability, and common environmental effect were computed for all probes (20.6%, 15.6%, and 5.0% respectively) and for probes showing a significant familial effect (78.1%, 60.1%, and 18.0% respectively). Pairwise phenotypic correlations between gene expression and DNA methylation levels adjusted for blood cell heterogeneity were computed for probes showing significant familial effect. A total of 78 probe pairs among the 7,618,401 possible pairs passed Bonferroni correction (corrected P-value = 6.56 × 10- 9). Significant genetic correlations between gene expression and DNA methylation levels were found for 25 probe pairs (absolute genetic correlation of 0.97). CONCLUSIONS: Familial resemblances in gene expression levels were mainly attributable to genetic factors, but common environmental effect also played a role especially in probes showing a significant familial effect. Probes and CpG sites with familial effect seem to be under a strong shared genetic control.

Yogurt consumption, body composition, and metabolic health in the Québec Family Study.

PURPOSE: The aim was to compare the anthropometric and metabolic profiles and lifestyle behaviours of yogurt consumers and non-consumers and to determine if the observed differences persisted after adjustment for diet quality and related variables. METHODS: Using cross-sectional and follow-up data from the Québec Family Study, men and women were classified into yogurt consumers (n = 269; 96 men and 173 women) and non-consumers (n = 570; 279 men and 291 women), and their anthropometric measurements, metabolic profiles, and lifestyle factors were compared. RESULTS: Men yogurt consumers had a lower body weight, BMI, % body fat, waist circumference and lower plasma insulin, and C-peptide concentrations in response to oral glucose, while women yogurt consumers had lower waist circumference, BMI, % body fat, plasma glucose, insulin, and C-peptide compared with non-consumers (P < 0.05). After adjustment for the Nutrient-Rich Foods (NRF) index, a marker of diet quality, these differences persisted in men and only for glycemic variables in women. Additional adjustment for physical activity participation and % body fat did not abolish the significant differences observed between yogurt consumers and non-consumers for plasma glucose, insulin, and C-peptide responses to oral glucose in women only (P < 0.05). Analyses of data after a 6-year follow-up reinforced these observations, since both men and women yogurt consumers maintained a better metabolic profile compared with non-consumers after adjustments for age and NRF (P < 0.05). In addition, an interaction between group and time for % body fat in men suggests a benefit of yogurt consumption over time on body composition. CONCLUSION: Yogurt consumption is associated with body composition and metabolic health benefits that are not entirely explained by a global effect of diet quality.

FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

Association between yogurt consumption, dietary patterns, and cardio-metabolic risk factors.

PURPOSE: To examine whether yogurt consumption is associated with a healthier dietary pattern and with a better cardio-metabolic risk profile among healthy individuals classified on the basis of their body mass index (BMI). METHODS: A 91-item food frequency questionnaire, including data on yogurt consumption, was administered to 664 subjects from the INFOGENE study. After principal component analysis, two factors were retained, thus classified as the Prudent and Western dietary patterns. RESULTS: Yogurt was a significant contributor to the Prudent dietary pattern. Moreover, yogurt consumption was associated with lower body weight, waist-to-hip ratio, and waist circumference and tended to be associated with a lower BMI. Consumers had lower levels of fasting total cholesterol and insulin. Consumers of yogurt had a positive Prudent dietary pattern mean score, while the opposite trend was observed in non-consumers of yogurt. Overweight/obese individuals who were consumers of yogurts exhibited a more favorable cardio-metabolic profile characterized by lower plasma triglyceride and insulin levels than non-consumers within the same range of BMI. There was no difference in total yogurt consumption between normal-weight individuals and overweight/obese individuals. However, normal-weight subjects had more daily servings of high-fat yogurt and less daily servings of fat-free yogurt compared to overweight/obese individuals. CONCLUSIONS: Being a significant contributor to the Prudent dietary pattern, yogurt consumption may be associated with healthy eating. Also, yogurt consumption may be associated with lower anthropometric indicators and a more beneficial cardio-metabolic risk profile in overweight/obese individuals.

A CpG-SNP Located within the ARPC3 Gene Promoter Is Associated with Hypertriglyceridemia in Severely Obese Patients.

AIMS: To test the potential association of cytosine-phosphate-guanine dinucleotides (CpG)-single-nucleotide polymorphisms (SNPs) located within actin-related protein 2/3 complex subunit 3 (ARPC3), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obese patients. METHODS: Prioritized SNPs within the ARPC3 locus were genotyped and tested for associations with MetS features in a cohort of 1,749 obese patients with and without MetS. Association testing with CpG methylation levels was performed in a methylation sub-cohort of 16 obese men. RESULTS: A significant association was found between the CpG-SNP rs3759384 (C>T) and plasma triglyceride (TG) levels (false discovery rate-corrected p = 3.5 × 10-2), with 0.6% of the phenotypic variance explained by the CpG-SNP, and with TT homozygotes showing the highest plasma TG levels (1.89 mmol/l). The carriers of the rs3759384 T allele also showed a significant decrease in methylation levels of the ARPC3 promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. ARPC3 expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02). CONCLUSIONS: The increased plasma TG levels found in homozygous rs3759384 T allele carriers argue for a relevant role of this CpG-SNP in lipid management among obese individuals, which may be driven by an epigenetic-mediated mechanism.

C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients.

Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences.

Differential methylation in visceral adipose tissue of obese men discordant for metabolic disturbances.

Obesity is associated with an increased risk of Type 2 diabetes and cardiovascular diseases (CVD). The severely obese population is heterogeneous regarding CVD risk profile. Our objective was to identify metabolic pathways potentially associated with development of metabolic syndrome (MetS) through an analysis of overrepresented pathways from differentially methylated genes between severely obese men with (MetS+) and without (MetS-) the MetS. Genome-wide quantitative DNA methylation analysis in VAT of severely obese men was carried out using the Infinium HumanMethylation450 BeadChip. Differences in methylation levels between MetS+ (n = 7) and MetS- (n = 7) groups were tested. Overrepresented pathways from the list of differentially methylated genes were identified and visualized with the Ingenuity Pathway Analysis system. Differential methylation analysis between MetS+ and MetS- groups identified 8,578 methylation probes (3,258 annotated genes) with significant differences in methylation levels (false discovery rate-corrected DiffScore ≥ |13| ∼ P ≤ 0.05). Pathway analysis from differentially methylated genes identified 41 overrepresented (P ≤ 0.05) pathways. The most overrepresented pathways were related to structural components of the cell membrane, inflammation and immunity and cell cycle regulation. This study provides potential targets associated with adipose tissue dysfunction and development of the MetS.

Cross-sectional associations of acylation stimulating protein (ASP) and adipose tissue gene expression with estradiol and progesterone in pre- and postmenopausal women.

OBJECTIVE: Sex steroid hormones play an important regulatory role in fat metabolism and obesity. We hypothesized involvement of interactions between ovarian hormones with acylation stimulating protein (ASP). DESIGN, PATIENTS AND MEASUREMENTS: In 392 women with wide age (18-69 years) and body size (BMI: 17 to 90 kg/m(2) ) ranges, fasting plasma levels of ASP, ovarian hormones, glucose, adiponectin and lipids/apolipoproteins were assessed, along with determination of metabolic syndrome (MS) features. Gene expression of C3 (ASP precursor) and related receptors C5L2, C3aR and C5aR in subcutaneous and omental adipose tissues was measured in a subset. RESULTS: Acylation stimulating protein correlated negatively with concentrations of estradiol (P < 0·0001), adiponectin (P < 0·001) and apolipoprotein A1 (P < 0·001) and positively with apolipoprotein B levels (P < 0·001), systolic blood pressure (P < 0·001), waist circumference (P < 0·001), and triglyceride concentrations (P < 0·01). In age-matched groups of lean, overweight, metabolically healthy obese (MHO) and obese with metabolic syndrome (MSO), there was a stepwise increase in ASP levels (P < 0·001) while concentrations of adiponectin (P < 0·0001) and estradiol (P < 0·001) but not those of progesterone decreased. Progesterone but not estradiol levels correlated positively with C3 gene expression in omental adipose tissue (P < 0·05) and negatively with C5L2 expression in both omental (P < 0·01) and subcutaneous (P < 0·05) adipose tissues. CONCLUSION: Our results are consistent with the concept that sex hormones differentially influence circulating ASP and adipose tissue gene expression of its related proteins in a depot-specific manner. ASP may play a role in the regulation of regional fat metabolism through interactions with sex hormones in women.

SREBF1 gene variations modulate insulin sensitivity in response to a fish oil supplementation.

BACKGROUND: An important inter-individual variability in the response of insulin sensitivity following a fish oil supplementation has been observed. The objective was to examine the associations between single nucleotide polymorphisms (SNPs) within sterol regulatory element binding transcription factor 1 (SREBF1) gene and the response of insulin sensitivity to a fish oil supplementation. METHODS: Participants (n = 210) were recruited in the greater Quebec City area and followed a 6-week fish oil supplementation protocol (5 g/day: 1.9-2.2 g EPA; 1.1 g DHA). Insulin sensitivity was assessed by the quantitative insulin sensitivity check index (QUICKI). Three tag SNPs (tSNPs) within SREBF1 gene were genotyped according to TAQMAN methodology. RESULTS: Three tSNPs (rs12953299, rs4925118 and rs4925115) covered 100% of the known genetic variability within SREBF1 gene. None of the three tSNPs was associated with either baseline fasting insulin concentrations (rs12953299, rs4925118 and rs4925115) (p = 0.29, p = 0.20 and p = 0.70, respectively) or QUICKI (p = 0.20, p = 0.18 and p = 0.76, respectively). The three tSNPs (rs12953299, rs4925118 and rs4925115) were associated with differences in the response of plasma insulin levels (p = 0.01, p = 0.005 and p = 0.004, respectively) and rs12953299 as well as rs4925115 were associated with the insulin sensitivity response (p = 0.009 and p = 0.01, respectively) to the fish oil supplementation, independently of the effects of age, sex and BMI. CONCLUSIONS: The genetic variability within SREBF1 gene has an impact on the insulin sensitivity in response to a fish oil supplementation. TRIAL REGISTRATION: clinicaltrials.gov: NCT01343342.

Sodium and Human Health: What Can Be Done to Improve Sodium Balance beyond Food Processing?

Sodium plays a key role in the regulation of water balance and is also important in food formulation due to its contribution to the taste and use in the preservation of many foods. Excessive intake of any essential nutrient is problematic and this seems to be particularly the case for sodium since a high intake makes it the nutrient most strongly associated with mortality. Sodium intake has been the object of recommendations by public health agencies such as the WHO and this has resulted in efforts by the food industry to reduce the sodium content of packaged foods, although there is still room for improvement. The recent literature also emphasizes the need for other strategies, e.g., regulations and education, to promote adequate sodium intake. In the present paper, we also describe the potential benefits of a global healthy lifestyle that considers healthy eating but also physical activity habits that improve body functionality and may help to attenuate the detrimental effects of high sodium intake on body composition and cardiometabolic health. In conclusion, a reduction in sodium intake, an improvement in body functioning, and educational interventions promoting healthy eating behaviours seem to be essential for the optimal regulation of sodium balance.

Impact of maternal cardiometabolic status after bariatric surgery on the association between telomere length and adiposity in offspring.

The impact of bariatric surgery on metabolic and inflammatory status are reflected in the epigenetic profile and telomere length mediated by the changes in the metabolic status of the patients. This study compared the telomere length of children born before versus after maternal bariatric surgery as a surrogate to test the influence of the mother's metabolic status on children's telomere length. DNA methylation telomere length (DNAmTL) was estimated from Methylation-EPIC BeadChip array data from a total of 24 children born before and after maternal bariatric surgery in the greater Quebec City area. DNAmTL was inversely associated with chronological age in children (r = - 0.80, p < 0.001) and significant differences were observed on age-adjusted DNAmTL between children born before versus after the maternal bariatric surgery. The associations found between body mass index and body fat percentage with DNAmTL in children born after the surgery were influenced by maternal triglycerides, TG/HDL-C ratio and TyG index. This study reports the impact of maternal bariatric surgery on offspring telomere length. The influence of maternal metabolic status on the association between telomere length and markers of adiposity in children suggests a putative modulating effect of bariatric surgery on the cardiometabolic risk in offspring.

Genetic control of body weight by the human brain proteome.

Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with body weight but the biological relevance of most remains unexplored. Given the critical role of the brain in body weight regulation, we set out to determine whether genetic variants linked with body mass index (BMI) could be mapped to brain proteins. Using genetic colocalization, we mapped 25 loci from the largest BMI GWAS (n = 806,834) to brain protein concentrations obtained from publicly available datasets. We also performed a proteome-wide Mendelian randomization on 696 brain proteins followed by genetic colocalization and identified 35 additional brain proteins. Only a minority of these proteins (<30%) had a colocalization signal with cortex gene expression levels, highlighting the value of moving beyond gene expression levels and examining brain protein levels. In conclusion, we identified 60 unique proteins expressed in the brain that may be critical regulators of body weight in humans.

Thymic stromal lymphopoietin: an immune cytokine gene associated with the metabolic syndrome and blood pressure in severe obesity.

A previous expression profiling of VAT (visceral adipose tissue) revealed that the TSLP (thymic stromal lymphopoietin) gene was less expressed in severely obese men with (n=7) compared with without (n=7) the MetS (metabolic syndrome). We hypothesized that TSLP SNPs (single nucleotide polymorphisms) are associated with TSLP gene expression in VAT and with MetS phenotypes. Following validation of lower TSLP expression (P=0.003) in VAT of severely obese men and women with (n=70) compared with without (n=60) the MetS, a detailed genetic investigation was performed at the TSLP locus by sequencing its promoter, exons and intron-exon splicing boundaries using DNA of 25 severely obese subjects. Five tagging SNPs were genotyped in the 130 subjects from the expression analysis to test whether these SNPs contributed to TSLP expression variability (ANOVAs) and then genotyped in two independent samples of severely obese men (total, n=389) and women (total, n=894). In a sex-stratified multistage experimental design, ANOVAs were performed to test whether tagging SNPs were associated with MetS components treated as continuous variables. We observed that the non-coding SNP rs2289277 was associated with TSLP mRNA abundance (P=0.04), as well as with SBP [systolic BP (blood pressure)] (P=0.004) and DBP (diastolic BP) (P=0.0003) in men when adjusting for age, waist circumference, smoking and medication treating hypertension. These novel observations suggest that TSLP expression in VAT may partly explain the inter-individual variability for metabolic impairments in the presence of obesity and that specific SNPs (rs2289277 and/or correlating SNPs) may influence TSLP gene expression as well as BP in obese men.

Past dieting is related to rigid control and disinhibition in adolescents from the Québec Family Study.

Eating behaviour traits of rigid control and disinhibition have been associated with body weight in both adults and adolescents. Moreover, adults reporting a dieting history have increased levels of unhealthy eating behaviours. Against this background, the present study aimed to examine the relationship between dieting history and eating behaviour traits in adolescents. For the purpose of this research, a total of sixty adolescents (aged 15 (sem 2·4) years) from the Québec Family Study completed the Three-Factor Eating Questionnaire (TFEQ) and a questionnaire regarding eating habits. Self-reported current and past dieting were analysed against eating behaviour traits measured by the TFEQ, including all subscales. As the results revealed, few adolescents reported currently dieting (n 3). Adolescents who reported a dieting history (23·3 %) were older (16·9 v. 14·4 years, P < 0·001), were more likely to be female (78·6 v. 41·3 %, P < 0·05) but did not have a significantly higher BMI z-score (1·5 v. 0·9, P = 0·10), although they were more likely to be either overweight or obese (P < 0·01). After correcting for sex, BMI and age, adolescents who reported a dieting history had higher levels of rigid control and disinhibition (P < 0·05-0·0001) than those reporting no dieting history. A greater proportion of adolescents characterised by high rigid control and high disinhibition were past dieters, compared to those characterised by low levels of both behaviour traits (53 v. 4 %). The study arrived at the following conclusions: as observed in adults, adolescents with a history of dieting present unfavourable eating behaviour traits. These behavioural traits may represent an additional challenge to the long-term regulation of body weight.