Genetic inhibition of angiopoietin-like protein-3, lipids, and cardiometabolic risk.

BACKGROUND AND AIMS: RNA-based, antibody-based, and genome editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3) could reduce lipoprotein-lipid levels and atherosclerotic cardiovascular disease (ASCVD) risk. Mendelian randomisation (MR) was used to determine whether genetic variations influencing ANGPTL3 liver gene expression, blood levels, and protein structure could causally influence triglyceride and apolipoprotein B (apoB) levels as well as coronary artery disease (CAD), ischaemic stroke (IS), and other cardiometabolic diseases. METHODS: RNA sequencing of 246 explanted liver samples and genome-wide genotyping was performed to identify single-nucleotide polymorphisms (SNPs) associated with liver expression of ANGPTL3. Genome-wide summary statistics of plasma protein levels of ANGPTL3 from the deCODE study (n = 35 359) were used. A total of 647 carriers of ANGPTL3 protein-truncating variants (PTVs) associated with lower plasma triglyceride levels were identified in the UK Biobank. Two-sample MR using SNPs that influence ANGPTL3 liver expression or ANGPTL3 plasma protein levels as exposure and cardiometabolic diseases as outcomes was performed (CAD, IS, heart failure, non-alcoholic fatty liver disease, acute pancreatitis, and type 2 diabetes). The impact of rare PTVs influencing plasma triglyceride levels on apoB levels and CAD was also investigated in the UK Biobank. RESULTS: In two-sample MR studies, common genetic variants influencing ANGPTL3 hepatic or blood expression levels of ANGPTL3 had a very strong effect on plasma triglyceride levels, a more modest effect on low-density lipoprotein cholesterol, a weaker effect on apoB levels, and no effect on CAD or other cardiometabolic diseases. In the UK Biobank, the carriers of rare ANGPTL3 PTVs providing lifelong reductions in median plasma triglyceride levels [-0.37 (interquartile range 0.41) mmol/L] had slightly lower apoB levels (-0.06 ± 0.32 g/L) and similar CAD event rates compared with non-carriers (10.2% vs. 10.9% in carriers vs. non-carriers, P = .60). CONCLUSIONS: PTVs influencing ANGPTL3 protein structure as well as common genetic variants influencing ANGPTL3 hepatic expression and/or blood protein levels exhibit a strong effect on circulating plasma triglyceride levels, a weak effect on circulating apoB levels, and no effect on ASCVD. Near-complete inhibition of ANGPTL3 function in patients with very elevated apoB levels may be required to reduce ASCVD risk.

Metabolic-associated fatty liver disease is characterized by a post-oral glucose load hyperinsulinemia in individuals with mild metabolic alterations.

Metabolic-associated fatty liver disease (MAFLD) has been identified as risk factor of incident type 2 diabetes (T2D), but the underlying postprandial mechanisms remain unclear. We compared the glucose metabolism, insulin resistance, insulin secretion, and insulin clearance post-oral glucose tolerance test (OGTT) between individuals with and without MAFLD. We included 50 individuals with a body mass index (BMI) between 25 and 40 kg/m2 and ≥1 metabolic alteration: increased fasting triglycerides or insulin, plasma glucose 5.5-6.9 mmol/L, or glycated hemoglobin 5.7-5.9%. Participants were grouped according to MAFLD status, defined as hepatic fat fraction (HFF) ≥5% on MRI. We used oral minimal model on a frequently sampled 3 h 75 g-OGTT to estimate insulin sensitivity, insulin secretion, and pancreatic ß-cell function. Fifty percent of participants had MAFLD. Median age (IQR) [57 (45-65) vs. 57 (44-63) yr] and sex (60% vs. 56% female) were comparable between groups. Post-OGTT glucose concentrations did not differ between groups, whereas post-OGTT insulin concentrations were higher in the MAFLD group (P < 0.03). Individuals with MAFLD exhibited lower insulin clearance, insulin sensitivity, and first-phase pancreatic ß-cell function. In all individuals, increased insulin incremental area under the curve and decreased insulin clearance were associated with HFF after adjusting for age, sex, and BMI (P < 0.02). Among individuals with metabolic alterations, the presence of MAFLD was characterized mainly by post-OGTT hyperinsulinemia and reduced insulin clearance while exhibiting lower first phase ß-cell function and insulin sensitivity. This suggests that MAFLD is linked with impaired insulin metabolism that may precede T2D.NEW & NOTEWORTHY Using an oral glucose tolerance test, we found hyperinsulinemia, lower insulin sensitivity, lower insulin clearance, and lower first-phase pancreatic ß-cell function in individuals with MAFLD. This may explain part of the increased risk of incident type 2 diabetes in this population. These data also highlight implications of hyperinsulinemia and impaired insulin clearance in the progression of MAFLD to type 2 diabetes.

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery.

BACKGROUND: Bariatric surgery is an effective therapy for individuals with severe obesity to achieve sustainable weight loss and to reduce comorbidities. Examining the molecular signature of subcutaneous adipose tissue (SAT) following different types of bariatric surgery may help in gaining further insight into their distinct metabolic impact. RESULTS: Subjects undergoing biliopancreatic diversion with duodenal switch (BPD-DS) showed a significantly higher percentage of total weight loss than those undergoing gastric bypass or sleeve gastrectomy (RYGB + SG) (41.7 ± 4.6 vs 28.2 ± 6.8%; p = 0.00005). Individuals losing more weight were also significantly more prone to achieve both type 2 diabetes and dyslipidemia remission (OR = 0.75; 95%CI = 0.51-0.91; p = 0.03). Whole transcriptome and methylome profiling showed that bariatric surgery induced a profound molecular remodeling of SAT at 12 months postoperative, mainly through gene down-regulation and hypermethylation. The extent of changes observed was greater following BPD-DS, with 61.1% and 49.8% of up- and down-regulated genes, as well as 85.7% and 70.4% of hyper- and hypomethylated genes being exclusive to this procedure, and mostly associated with a marked decrease of immune and inflammatory responses. Weight loss was strongly associated with genes being simultaneously differentially expressed and methylated in BPD-DS, with the strongest association being observed for GPD1L (r2 = 0.83; p = 1.4 × 10-6). CONCLUSIONS: Present findings point to the greater SAT molecular remodeling following BPD-DS as potentially linked with higher metabolic remission rates. These results will contribute to a better understanding of the metabolic pathways involved in the response to bariatric surgery and will eventually lead to the development of gene targets for the treatment of obesity. Trial registration ClinicalTrials.gov NCT02390973.

Towards a Standardized Definition of Medical Nutrition Therapy and Regulatory Reform in Canada.

Various definitions have been proposed to describe Medical Nutrition Therapy (MNT). Broadly, MNT encompasses the provision of nutrition information and advice aimed to prevent, treat, and/or manage health conditions. In Canada, the provision of such information and advice is unregulated, thus allowing anyone to provide MNT services regardless of their education and training. This inevitably poses risks of harm such as the provision of unsafe and/or ineffective nutrition advice as well as delayed evidence-based treatment. Canadian research has further demonstrated that the general public is unable to properly differentiate between regulated, evidence-based nutrition providers (registered dietitians) and those who are unregulated. Therefore, the public is at risk. To reduce nutrition misinformation and ultimately improve the health and well-being of the public, the objective of this paper is, first, to propose a standardized definition of MNT for use across Canada and, second, to propose province- and territory-specific legislative amendments for the regulation of MNT throughout the country. We also present an opposing perspective to the proposed viewpoint. Ultimately, health care regulation across the country requires an overhaul before we expect that nutrition information and advice communicated to the public may be consistently evidence based.

Cholecalciferol Supplementation Does Not Prevent the Development of Metabolic Syndrome or Enhance the Beneficial Effects of Omega-3 Fatty Acids in Obese Mice.

BACKGROUND: Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood. OBJECTIVES: We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice. METHODS: We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA. RESULTS: D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa. CONCLUSIONS: Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice.

Associations of Intake of Free and Naturally Occurring Sugars from Solid Foods and Drinks with Cardiometabolic Risk Factors in a Quebec Adult Population: The PREDISE (PRÉDicteurs Individuels, Sociaux et Environnementaux) Study.

BACKGROUND: Associations between sugar consumption and cardiometabolic health, taking into account the physical form of sugar-containing foods (liquid vs. solid) and the type of sugars consumed [free sugars (FSs) vs. naturally occurring sugars (NOSs)], remain to be thoroughly documented. OBJECTIVE: The objective was to examine whether FS and NOS intakes from drinks and solid foods are associated with cardiometabolic risk factors in a sample of French-speaking adults from the province of Quebec, Canada. METHODS: Data were collected as part of the cross-sectional PREDISE (PRÉDicteurs Individuels, Sociaux et Environnementaux) study (n = 1019, 18-65 y old; 50% women). FS and NOS intakes were assessed by three 24-h dietary recalls using a self-administered, web-based application. Diet quality was assessed using the Alternative Healthy Eating Index-2010. Participants underwent on-site clinical assessment of cardiometabolic risk factors, including blood pressure, waist circumference, BMI, and fasting blood sampling (glucose, insulin, C-reactive protein, blood lipids). Multivariable linear regression models were performed to examine the associations between sugar intake and cardiometabolic risk factors with sociodemographic characteristics, lifestyle variables, and diet quality entered as covariates. RESULTS: In fully adjusted models, FS intake from drinks was associated with fasting insulin (1.06%; 95% CI: 0.30%, 1.84%; P = 0.006) and with insulin resistance as estimated using the HOMA model (1.01%; 95% CI: 0.19%, 1.84%; P = 0.02). All metabolic variables that were significantly associated with NOS intake from solid foods in minimally adjusted models were no longer significant after entering sociodemographic and lifestyle variables (e.g., educational and income levels, smoking, physical activity, daily energy intake) and diet quality in the models. CONCLUSIONS: Our data from an adult sample showed that unfavorable and favorable associations with cardiometabolic risk factors observed, respectively, for FS intake from drinks and NOS intake from foods are mostly explained by sociodemographic and lifestyle variables, as well as by diet quality.

Individuals with self-determined motivation for eating have better overall diet quality: Results from the PREDISE study.

The study aimed at documenting motivational orientations for the regulation of eating as defined by self-determination theory and their association with sociodemographic characteristics and overall diet quality. As part of the PREDISE study, French-speaking women (n = 550) and men (n = 547), aged 18-65 years, living in the Province of Québec, Canada, completed online validated questionnaires. The Regulation of Eating Behavior Scale, based on the self-determination theory, assessed self-determined and non-self-determined motivation to regulate one's eating behavior. Three web-based 24-h food recalls were completed and used to compute the Canadian Healthy Eating Index 2007 (C-HEI), an indicator of the overall adherence to Canadian guidelines for healthy eating. Multiple linear regressions were performed to assess how regulation styles are associated with the C-HEI. Model 1 included no covariate, model 2 included sociodemographic covariates, and fully adjusted model 3 included as covariates sociodemographic variables as well as variables that were previously associated with diet quality, namely nutrition knowledge and social support for healthy eating. Women (p < 0.0001), older individuals (p = 0.0002), those with a higher education level (p < 0.0001), and non-smokers (p < 0.0001) reported higher self-determined motivation score than their counterparts. Self-determined motivation was positively (model 1: B = 4.67, p < 0.0001; model 2: B = 3.82, p < 0.0001; model 3: B = 3.61, p < 0.0001) and non-self-determined motivation was negatively (model 1: B = -1.62, p = 0.0009; model 2: B = -1.63, p = 0.0006; model 2: B = -1.49, p = 0.0022) associated with C-HEI. The present study suggests that some subgroups of the general adult population show more self-determined motivation for eating, which is associated with a better diet quality independently of individual characteristics and other individual and social determinants of healthy eating. Strategies to help individuals internalize the regulation of eating should be further investigated.

Biological plausibility for interactions between dietary fat, resveratrol, ACE2, and SARS-CoV illness severity.

The angiotensin converting enzyme-2 (ACE2) cellular receptor is responsible for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus impacting the entrance and clearance of the virus. Studies demonstrate that upregulation of ACE2 has a protective effect on SARS-CoV-2 illness severity. Moreover, animal studies demonstrate that dietary intake can modulate ACE2 gene expression and function. A high intake of resveratrol may have a protective role, upregulating ACE2, whereas a high intake of dietary fat may have a detrimental role, downregulating ACE2. As such, we postulate on the biological plausibility of interactions between dietary fat and/or resveratrol and ACE2 gene variations in the modulation of SARS-CoV-2 illness severity. We call to action the research community to test this plausible interaction in a sample of human subjects.

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.

Correlates of the difference in plasma carotenoid concentrations between men and women.

Health professionals consider the evaluation of eating habits to be challenging, given the potential biases of dietary questionnaires based on self-reported data. Circulating carotenoid concentrations are reliable biomarkers of dietary carotenoid intake and could be useful in the validation of dietary assessment tools. However, there is a sex difference in circulating carotenoids, with women displaying higher concentrations compared with men independent of intake. The aim of the present study was to identify the correlates of plasma carotenoid concentrations among men (n 155) and women (n 110) enrolled in six fully controlled dietary interventions with varying dietary carotenoid intakes. We looked at the associations of post-intervention fasting plasma carotenoid concentrations (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, lycopene and zeaxanthin) with physical and metabolic characteristics. We found that increased body weight (r -0·47, P<0·0001) and waist circumference (r -0·46, P<0·0001) were associated with lower plasma total carotenoid concentrations, while elevated plasma LDL-cholesterol (r 0·49, P<0·0001) and HDL-cholesterol (r 0·50, P<0·0001) concentrations were correlated with higher total carotenoids in plasma. Women had significantly higher plasma total carotenoid concentrations compared with men, despite significantly lower dietary carotenoid intake. Adjustment of circulating carotenoid concentrations for plasma HDL-cholesterol eliminated sex difference in plasma carotenoid concentrations. Our results suggest that physical characteristics as well as plasma lipids are associated with circulating carotenoid concentrations and that these variables should be taken into account when using plasma carotenoids as biomarkers for food intake in men and women.

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.

Consumption of low nutritive value foods and cardiometabolic risk factors among French-speaking adults from Quebec, Canada: the PREDISE study.

BACKGROUND: There is very limited knowledge on the magnitude to which foods with low nutritive value constitute the diet of adults from the province of Quebec. The extent to which these foods impact cardiometabolic risk is also poorly documented. The objective was to assess the contribution of low nutritive value foods to total energy intake (E) and to examine associations with cardiometabolic risk factors among French-speaking adults from 5 administrative regions of the Province of Quebec. METHODS: As part of the cross-sectional PREDISE Study, 1147 adults (50.2% women; mean [SD] age, 43.2 [4.6] years) participated in a web-based investigation. Dietary intake data were obtained using a validated web-based self-administered 24-h recall, the R24W, completed on three occasions. Foods with low nutritive value were defined as foods exceeding predetermined thresholds for the following nutrients: saturated fat, sugar or sodium as well as beverages and ingredients not recommended in Canada's Food Guide 2019. A total of 1019 participants underwent on-site clinical assessment of cardiometabolic risk factors. RESULTS: Participants consumed on average 29.0%E (95%CI, 28.2-29.7) as low nutritive value foods, to which pastries (18%), alcohol (15%), sweets (13%), chips/popcorn (6%) and sugar-sweetened beverages (6%) contributed the most. Low nutritive value foods contributed more to total E in men than in women (30.7%E vs. 27.5%E, respectively; P < 0.0001). In fully-adjusted linear regression models, increments of 250 kcal/d from low nutritive value foods were associated with higher body mass index (+ 1.7 kg/m2; 95%CI 1.2 to 2.2), higher waist circumference (+ 0.6 cm; 95%CI, 0.1 to 1.1), cholesterol: HDL cholesterol ratio (+ 0.12 mmol/L; 95%CI, 0.01 to 0.24 and triglycerides (+ 7.8%; 95%CI, 3.0 to 12.8). CONCLUSIONS: Low nutritive value foods contribute near 30% of total daily energy intake of French-speaking adults of the Province of Quebec and are associated with increased waist circumference and an unfavourable lipid profile. Addressing consumption of low nutritive value foods at the population level is a potential strategy to attenuate the burden of chronic diseases.

Acute Effects of Single Doses of Bonito Fish Peptides and Vitamin D on Whole Blood Gene Expression Levels: A Randomized Controlled Trial.

Fish contains high quality proteins and essential nutrients including 25-hydroxyvitamin D (25(OH)D). Fish peptide consumption can lower cardiovascular disease (CVD) risk factors, and studies have shown an association between 25(OH)D deficiency, CVD and CVD risk factors, such as diabetes. This study investigated acute effects of a single dose of cholecalciferol (VitD3), bonito fish peptide hydrolysate (BPH), or a combination of both on CVD risk factors and whole blood gene expression levels. A randomized, crossover, placebo controlled trial was conducted in 22 adults. They ingested, in random order and at 7-day intervals, 1000 IU of VitD3, 3 g of BPH, a combination of both, or a placebo. A 180 min oral glucose tolerance test was performed. Differences in whole-genome expression levels after versus before each supplementation were computed for 18 subjects. We observed that 16, 1 and 5 transcripts were differentially expressed post- vs. pre-ingestion for VitD3, BPH or VitD3 + BPH treatments, respectively. VitD3-containing treatments affected the expression of the solute carrier family 25 member 20 (SLC25A20) gene involved in fatty acid oxidation, various transcription factors and genes related to glucose metabolism. These results suggest that VitD3 rapidly modulates genes related to CVD risk factors in blood while BPH seems to moderately modulate gene expression levels.

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.

Supplementation with Resveratrol and Curcumin Does Not Affect the Inflammatory Response to a High-Fat Meal in Older Adults with Abdominal Obesity: A Randomized, Placebo-Controlled Crossover Trial.

Background: High-fat meals induce postprandial inflammation. Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action. There is also an increasing body of evidence supporting the role of curcumin, a polyphenol from the curcuminoid family, as a modulator of proinflammatory processes. Objective: The objectives of this study were to investigate the following: 1) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal; and 2) the acute combined effects of this combination on the postprandial inflammatory response of subjects with abdominal obesity. Methods: In a double blind, crossover, randomized, placebo-controlled study, 11 men and 11 postmenopausal women [mean ± SD age: 62 ± 5 y; mean ± SD body mass index (in kg/m2): 29 ± 3] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1-2 wk: once after consumption of a dietary supplement (200 mg resveratrol and 100 mg curcumin, Res/Cur) and once after consumption of a placebo (cellulose). Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers, adhesion molecules, and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests. Results: Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations. Supplementation with Res/Cur did not modify postprandial variations in circulating inflammatory markers (C-reactive protein, IL-6, IL-8, monocyte chemoattractant protein-1) and adhesion molecules [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1] compared to placebo (PTreatment×Time > 0.05). However, Res/Cur significantly decreased the cumulative postprandial response of sVCAM-1, compared to placebo (incremental area under the curve -4643%, P = 0.01). Postprandial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments. Conclusions: Acute supplementation with Res/Cur has no impact on the postprandial inflammation response to a high-fat meal in abdominally obese older adults. Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal. This trial was registered at clinicaltrials.gov as NCT01964846.

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.

Social support for healthy eating: development and validation of a questionnaire for the French-Canadian population.

OBJECTIVE: The present study aimed to develop and validate a questionnaire assessing social support for healthy eating in a French-Canadian population. DESIGN: A twenty-one-item questionnaire was developed. For each item, participants were asked to rate the frequency, in the past month, with which the actions described had been done by family and friends in two different environments: (i) at home and (ii) outside of home. The content was evaluated by an expert panel. A validation study sample was recruited and completed the questionnaire twice. Exploratory factor analysis was performed on items to assess the number of subscales. Internal consistency reliability was assessed using Cronbach's ɑ. Test-retest reliability was evaluated with intraclass correlations between scores of the two completions. SETTING: Online survey. SUBJECTS: Men and women from the Québec City area (n 150). RESULTS: The content validity assessment led to a few changes, resulting in a twenty-two-item questionnaire. Exploratory factor analysis revealed a two-factor structure for both environments, resulting in four subscales: supportive actions at home; non-supportive actions at home; supportive actions outside of home; and non-supportive actions outside of home. Two items were removed from the questionnaire due to low loadings. The four subscales were found to be reliable (Cronbach's ɑ=0·82-0·94; test-retest intraclass correlation=0·51-0·70). CONCLUSIONS: The Social Support for Healthy Eating Questionnaire was developed for a French-Canadian population and demonstrated good psychometric properties. This questionnaire will be useful to explore the role of social support and its interactions with other factors in predicting eating behaviours.

Development and validation of a nutrition knowledge questionnaire for a Canadian population.

OBJECTIVE: The present study aimed to develop and validate a nutrition knowledge questionnaire in a sample of French Canadians from the province of Quebec, taking into account dietary guidelines. DESIGN: A thirty-eight-item questionnaire was developed by the research team and evaluated for content validity by an expert panel, and then administered to respondents. Face validity and construct validity were measured in a pre-test. Exploratory factor analysis and covariance structure analysis were performed to verify the structure of the questionnaire and identify problematic items. Internal consistency and test-retest reliability were evaluated through a validation study. SETTING: Online survey. SUBJECTS: Six nutrition and psychology experts, fifteen registered dietitians (RD) and 180 lay people participated. RESULTS: Content validity evaluation resulted in the removal of two items and reformulation of one item. Following face validity, one item was reformulated. Construct validity was found to be adequate, with higher scores for RD v. non-RD (21·5 (sd 2·1) v. 15·7 (sd 3·0) out of 24, P<0·001). Exploratory factor analysis revealed that the questionnaire contained only one factor. Covariance structure analysis led to removal of sixteen items. Internal consistency for the overall questionnaire was adequate (Cronbach's α=0·73). Assessment of test-retest reliability resulted in significant associations for the total knowledge score (r=0·59, P<0·001). CONCLUSIONS: This nutrition knowledge questionnaire was found to be a suitable instrument which can be used to measure levels of nutrition knowledge in a Canadian population. It could also serve as a model for the development of similar instruments in other populations.

Plasma Triglyceride Levels May Be Modulated by Gene Expression of IQCJ, NXPH1, PHF17 and MYB in Humans.

A genome-wide association study (GWAS) by our group identified loci associated with the plasma triglyceride (TG) response to ω-3 fatty acid (FA) supplementation in IQCJ, NXPH1, PHF17 and MYB. Our aim is to investigate potential mechanisms underlying the associations between single nucleotide polymorphisms (SNPs) in the four genes and TG levels following ω-3 FA supplementation. 208 subjects received 3 g/day of ω-3 FA (1.9-2.2 g of EPA and 1.1 g of docosahexaenoic acid (DHA)) for six weeks. Plasma TG were measured before and after the intervention. 67 SNPs were selected to increase the density of markers near GWAS hits. Genome-wide expression and methylation analyses were conducted on respectively 30 and 35 participants' blood sample together with in silico analyses. Two SNPs of IQCJ showed different affinities to splice sites depending on alleles. Expression levels were influenced by genotype for one SNP in NXPH1 and one in MYB. Associations between 12 tagged SNPs of IQCJ, 26 of NXPH1, seven of PHF17 and four of MYB and gene-specific CpG site methylation levels were found. The response of plasma TG to ω-3 FA supplementation may be modulated by the effect of DNA methylation on expression levels of genes revealed by GWAS.

Carotenoids as biomarkers of fruit and vegetable intake in men and women.

High fruit and vegetable (FAV) intake is associated with a lower prevalence of chronic diseases. Identifying the ideal number of FAV servings needed to reduce chronic disease risk is, however, difficult because of biases inherent to common self-report dietary assessment tools. The aim of our study was to examine the associations between daily FAV intake and plasma carotenoid concentrations in men and women enrolled in a series of fully controlled dietary interventions. We compiled and analysed data from a group of 155 men and 109 women who participated in six fully controlled dietary interventions and compared post-intervention fasting plasma carotenoid (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, lycopene, zeaxanthin) concentrations with regard to the daily FAV servings consumed by the participants. We found that plasma ß-cryptoxanthin, lutein and zeaxanthin concentrations were positively associated with daily FAV servings (P≤0·005). However, daily FAV intake was negatively associated with plasma α-carotene (P<0·0005) and lycopene (P<0·0001) concentrations, whereas no association was noted with plasma ß-carotene. When men and women were analysed separately, we found that for any given number of FAV servings consumed women had higher circulating lutein concentrations compared with men (P<0·01). Significant sex×FAV (P<0·0001) and sex×dietary ß-cryptoxanthin (P<0·0005) interactions were also noted favouring higher plasma ß-cryptoxanthin concentrations in women than in men for a given FAV consumption. Results from these fully controlled dietary feeding studies indicate that plasma ß-cryptoxanthin and lutein concentrations can be used as robust biomarkers of FAV consumption. They also suggest the existence of sex differences influencing circulating ß-cryptoxanthin and lutein concentrations following FAV consumption.