BACKGROUND: Increased consumption of dietary fiber is widely recommended to maintain or improve health, but knowledge of the relation between dietary fiber sources and cardiovascular disease risk ...factors is limited. OBJECTIVE: We examined the relation between the source or type of dietary fiber intake and cardiovascular disease risk factors in a cohort of adult men and women. DESIGN: In a cross-sectional study, quintiles of fiber intake were determined from dietary records, separately for 2532 men and 3429 women. Age- and multivariate-controlled logistic models investigated the odds ratios of abnormal markers for quintiles 2-5 of fiber intake compared with the lowest quintile. RESULTS: The highest total dietary fiber and nonsoluble dietary fiber intakes were associated with a significantly (P < 0.05) lower risk of overweight and elevated waist-to-hip ratio, blood pressure, plasma apolipoprotein (apo) B, apo B:apo A-I, cholesterol, triacylglycerols, and homocysteine. Soluble dietary fiber was less effective. Fiber from cereals was associated with a lower body mass index, blood pressure, and homocysteine concentration; fiber from vegetables with a lower blood pressure and homocysteine concentration; and fiber from fruit with a lower waist-to-hip ratio and blood pressure. Fiber from dried fruit or nuts and seeds was associated with a lower body mass index, waist-to-hip ratio, and fasting apo B and glucose concentrations. Fiber from pulses had no specific effect. CONCLUSION: Dietary fiber intake is inversely correlated with several cardiovascular disease risk factors in both sexes, which supports its protective role against cardiovascular disease and recommendations for its increased consumption.
Signal transducer and activator of transcription 3 (STAT3) plays a key role in body weight regulation and glucose homeostasis, 2 important determinants of metabolic syndrome (MetS). Dietary fat is a ...key environmental factor that may interact with genotype to affect MetS risk. In this study, we investigated the relationship between STAT3 polymorphisms and MetS phenotypes and determined potential interactions with dietary fatty acids. STAT3 polymorphisms (rs8069645, rs744166, rs2306580, rs2293152, and rs10530050), biochemical measurements, and dietary fat composition were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). STAT3 polymorphisms were not associated with MetS risk. However, minor G allele carriers for rs8069645, rs744166, and rs1053005 and major GG homozygotes for rs2293152 had increased risk of abdominal obesity compared with noncarriers odds ratio (OR) = 2.22, P = 0.0005; OR = 2.08, P = 0.0017; OR = 2.00, P = 0.0033; and OR = 1.95, P = 0.028, respectively. The number of risk alleles additively increased obesity risk (P = 0.0003). Dietary SFA intake exacerbated these effects; among all participants with the highest SFA intake (greater-than-or-equal15.5% of energy), individuals carrying >2 risk alleles had further increased risk of obesity (OR = 3.30; 95% CI = 1.50-7.28; P = 0.0079) compared with those carrying less-than or equal to1 risk allele. Interaction analysis confirmed this gene-nutrient interaction whereby increasing SFA intake was predictive of increased waist circumference (P = 0.038). In conclusion, STAT3 gene polymorphisms influenced the risk of abdominal obesity, which is modulated by dietary SFA intake, suggesting novel gene-nutrient interactions.
Long-chain acyl CoA synthetase 1 (ACSL1) plays an important role in fatty acid metabolism and triacylglycerol (TAG) synthesis. Disturbance of these pathways may result in dyslipidemia and insulin ...resistance, hallmarks of the metabolic syndrome (MetS). Dietary fat is a key environmental factor that may interact with genetic determinants of lipid metabolism to affect MetS risk. We investigated the relationship between ACSL1 polymorphisms (rs4862417, rs6552828, rs13120078, rs9997745, and rs12503643) and MetS risk and determined potential interactions with dietary fat in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1,754). GG homozygotes for rs9997745 had increased MetS risk {odds ratio (OR) 1.90 confidence interval (CI) 1.15, 3.13; P = 0.01}, displayed elevated fasting glucose (P = 0.001) and insulin concentrations (P = 0.002) and increased insulin resistance (P = 0.03) relative to the A allele carriers. MetS risk was modulated by dietary fat, whereby the risk conferred by GG homozygosity was abolished among individuals consuming either a low-fat (<35% energy) or a high-PUFA diet (>5.5% energy). In conclusion, ACSL1 rs9997745 influences MetS risk, most likely via disturbances in fatty acid metabolism, which was modulated by dietary fat consumption, particularly PUFA intake, suggesting novel gene-nutrient interactions.
LVP1, a novel protein inducing lipolytic response in adipose cells, was purified from scorpion
Buthus occitanus tunetanus venom. It represented 1% of crude venom proteins, with pHi∼6 and molecular ...mass of 16
170 Da. In contrast to well-characterized scorpion toxins, reduction and alkylation of LVP1 revealed an heterodimeric structure. Isolated α and β chains of LVP1 have a respective molecular mass of 8877 and 8807 Da as determined by mass spectrometry. The N-terminal and some internal peptide sequences of LVP1α and β were determined by Edman degradation. The full amino acid sequences of both chains were deduced from nucleotide sequences of the corresponding cDNAs prepared based on peptide sequences and the 3′ and 5′ RACE methodologies. LVP1α and β cDNAs encode a signal peptide of 22 residues and a mature peptide of 69 and 73 residues, respectively. Each mature peptide contains seven cysteines, which are compatible with an interchain disulfide bridge. The cDNA deduced protein structures share a high similarity with those of some Na
+ channel scorpion toxins. LVP1 was not toxic to mice after intracerebro-ventricular injection. LVP1 stimulated lipolysis on freshly dissociated rat adipocytes in a dose-dependent manner with EC50 of ∼1+0.5 μg/ml. LVP1 subunits did not display any lipolytic activity. As previously described for venom, β adrenergic receptor (β AR) antagonists interfere with LVP1 activity. Furthermore, it is shown that LVP1 competes with
3H-CGP 12177 (β
1/β
2 antagonist) for binding to adipocyte plasma membrane with an IC50 of about 10
−7 M. These results demonstrate the existence of a new type of scorpion venom nontoxic peptides that are structurally related to Na
+ channel toxins but can exert a distinct biological activity on adipocyte lipolysis through a β-type adrenoreceptor pathway.
Fat mass and obesity-associated (FTO) is the strongest genetic determinant of obesity identified to date. Dietary fat is a key environmental factor that may interact with genotype to affect risk of ...obesity and metabolic syndrome (MetS). This study investigated associations among FTO rs9939609, obesity measures, and MetS phenotypes in adults and determined potential modulation by dietary fat intake at baseline and after a 7.5-y follow-up when MetS cases and controls were selected. FTO rs9939609 genotype, biochemical, dietary, and lifestyle measurements were determined in the LIPGENE-SU.VI.MAX study (n = 1754). FTO rs9939609 A allele carriers had a higher risk of being overweight or obese OR = 1.66 (95% CI: 1.07, 2.57); P = 0.02 and of having a larger abdominal circumference OR = 1.42 (95% CI: 1.01, 1.99); P = 0.04 compared with the TT homozygotes. These associations were independent of physical activity and energy intake and were maintained over the follow-up period, particularly in the MetS individuals. High dietary SFA intake (≥ 15.5% energy) and a low dietary PUFA:SFA intake ratio (<0.38) further accentuated the risk of having a BMI ≥ 25 kg/m(2) and being abdominally obese. Non-risk allele carriers appeared to be unresponsive to dietary SFA intake or to the dietary PUFA:SFA intake ratio with respect to obesity measures. In conclusion, FTO rs9939609 was associated with obesity measures, especially in those with the MetS, which was further exacerbated by high dietary SFA intake at baseline and 7.5 y later. These data indicate important novel modulation of genetic risk by dietary fat exposure in individuals with increased cardiometabolic risk.
Context:
The postprandial chylomicron (CM) triacylglycerol (TG) response to dietary fat, which is positively associated with atherosclerosis and cardiovascular disease risk, displays a high ...interindividual variability. This is assumed to be due, at least partly, to polymorphisms in genes involved in lipid metabolism. Existing studies have focused on single nucleotide polymorphisms (SNPs), resulting in only a low explained variability.
Objective:
We aimed to identify a combination of SNPs associated with the postprandial CM TG response.
Participants and Methods:
Thirty-three healthy male volunteers were subjected to 4 standardized fat tolerance test meals (to correct for intraindividual variability) and genotyped using whole-genome microarrays. The plasma CM TG concentration was measured at regular interval times after each meal. The association of SNPs in or near candidate genes (126 genes representing 6225 SNPs) with the postprandial CM TG concentration (0–8 h areas under the curve averaged for the 4 test meals) was assessed by partial least squares regression, a multivariate statistical approach.
Results:
Data obtained allowed us to generate a validated significant model (P = 1.3 × 10−7) that included 42 SNPs in 23 genes (ABCA1, APOA1, APOA5, APOB, BET1, CD36, COBLL1, ELOVL5, FRMD5, GPAM, INSIG2, IRS1, LDLR, LIPC, LPL, LYPLAL1, MC4R, NAT2, PARK2, SLC27A5, SLC27A6, TCF7L2, and ZNF664) and explained 88% of the variance. In 39 of these SNPs, univariate analysis showed that subjects with different genotypes exhibited significantly different (q < .05) postprandial CM TG responses.
Conclusions:
Using a multivariate approach, we report a combination of SNPs that explains a significant part of the variability in the postprandial CM TG response.
BACKGROUND: Epidemiologic studies link Mediterranean-type diets to a low incidence of cardiovascular disease; however, few dietary intervention studies have been undertaken, especially in primary ...prevention. OBJECTIVES: In the Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms (Medi-RIVAGE) study, the effects of a Mediterranean-type diet (Med group) or a low-fat diet (low-fat group) on risk factors were evaluated in 212 volunteers (men and women) with moderate risk factors for cardiovascular disease. DESIGN: After the 3-mo dietary intervention, changes in many risk factors were evaluated. Dietary questionnaires and plasma nutritional markers were used to test compliance. RESULTS: Although the dietary goals were only partially reached, changes in dietary habits were observed in both groups (n = 169): protein, carbohydrate, and fiber intakes increased and fat quality (decreased saturated fat and increased monounsaturated or polyunsaturated fat) improved. BMI, total and triacylglycerol-rich lipoprotein (TRL) cholesterol, triacylglycerols, TRL triacylglycerols, apolipoproteins A-I and B, insulinemia, glycemia, and the homeostasis model assessment score were significantly lower after 3 mo. The reductions in total cholesterol, triacylglycerols, and insulinemia remained significant after adjustment for BMI. There was a trend for a diet-by-time interaction for LDL cholesterol (P = 0.09). Our data predicted a 9% reduction in cardiovascular disease risk with the low-fat diet and a 15% reduction with this particular Mediterranean diet. CONCLUSION: After a 3-mo intervention, both diets significantly reduced cardiovascular disease risk factors to an overall comparable extent.
Vitamin E and carotenoids are fat-soluble micronutrients carried by plasma lipoproteins. Their plasma concentrations are governed by several factors, some of which are genetic, but data on these ...genetic factors remain scarce. We hypothesized that genes involved in lipid metabolism, i.e. the genes implicated in intestinal uptake, intracellular trafficking, and the lipoprotein distribution of lipids, play a role in the plasma concentrations of these micronutrients. To verify this hypothesis, we assessed whether the plasma status of vitamin E and carotenoids is related to genes involved in lipid metabolism. Fasting plasma vitamin E (α- and γ-tocopherol) and carotenoid (α- and β-carotene, lutein, lycopene, β-cryptoxanthin, and zeaxanthin) concentrations were measured in 48 males and 80 females. The following genes were genotyped single nucleotide polymorphisms (SNP): apolipoprotein (apo) A-IV, apo B, apo E, lipoprotein lipase, and scavenger-receptor class B type I (SR-BI). Plasma α-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV, apo E, and SR-BI. Plasma γ-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and SR-BI. α-Carotene concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. β-Carotene concentrations were different (P < 0.05) in subjects bearing different SNP in apo B and SR-BI. Lycopene concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and apo B. β-Cryptoxanthin concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. Plasma lutein and zeaxanthin concentrations did not differ in subjects bearing different SNP. Most of the differences remained significant after the plasma micronutrients were adjusted for plasma triglycerides and cholesterol. These results suggest that genes involved in lipid metabolism influence the plasma concentrations of these fat-soluble micronutrients.
Abstract Objective Chronic inflammation plays a role in the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease (CVD). Complement component 3 (C3) is a novel cardiometabolic risk ...factor. Whether dietary fat intake modulates MetS risk conferred by elevated C3 concentrations is unknown. Our objective is to investigate the relationship between C3 concentrations and risk of the MetS and its phenotypes, and to further examine whether dietary fat intake modulates these relationships. Methods Biochemical, dietary and lifestyle measurements were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls ( n = 1754). Results Elevated C3 concentrations (>median) were associated with increased risk of impaired insulin sensitivity OR 1.78, CI 1.34–2.36, P < 0.0001, insulin resistance OR 1.73, CI 1.31–2.89, P = 0.0001, abdominal obesity OR 2.15, CI 1.43–3.24, P = 0.0002 and low HDL cholesterol OR 1.40, CI 1.05–1.86, P = 0.02 compared to low C3 concentrations. Increased MetS risk conferred by elevated C3 concentrations OR 3.11, 95% CI 2.52–3.82, P < 0.0001 was further accentuated among high dietary fat consumers OR 4.80, 95% CI 2.77–8.33, P < 0.0001 (particularly of saturated OR 4.05, 95% CI 2.33–7.05, P < 0.0001 and monounsaturated fat OR 4.48, 95% CI 2.62–7.56, P < 0.0001), and smokers OR 3.83, 95% CI 2.12–6.94, P < 0.0001, however this effect was abolished in abdominally lean individuals OR 1.46, 95% CI 0.69–3.14, P = 0.33. Conclusions Dietary fat (intake and composition), abdominal obesity and smoking modulate the relationship between elevated plasma C3 concentrations and MetS risk.
Transcription factor 7-like 2 (TCF7L2) is the strongest genetic determinant of type 2 diabetes (T2DM) and insulin-related phenotypes to date. Dietary fat is a key environmental factor which may ...interact with genotype to affect risk of metabolic syndrome (MetS) and T2DM. This study investigated the relationship between the TCF7L2 rs7903146 polymorphism, insulin sensitivity/resistance and MetS in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n=1754) and determined potential interactions with dietary fat intake. Female minor T allele carriers of rs7903146 had increased MetS risk (odds ratio OR 1.66, confidence interval CI 1.02–2.70, P=.04) and displayed elevated insulin concentrations (P=.005), impaired insulin sensitivity (P=.011), increased abdominal obesity (P=.008) and body mass index (P=.001) and higher blood pressure (P<.05) compared to the CC homozygotes. Metabolic syndrome risk was also modulated by dietary saturated fat (SFA) intake (P=.035 for interaction). High dietary SFA intake (≥15.5% energy) exacerbated MetS risk (OR 2.35, 95% CI 1.29–4.27, P=.005) and was associated with further impaired insulin sensitivity in the T allele carriers relative to the CC homozygotes (P=.025) and particularly to the T allele carriers with the lowest SFA intake (P=.008). No significant genotype effect on MetS risk or insulin sensitivity was evident among low-SFA consumers. In conclusion, the TCF7L2 rs7903146 polymorphism influences MetS risk, which is augmented by both gender and dietary SFA intake, suggesting novel gene–diet–gender interactions.
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