Gene-diet interaction of a common FADS1 variant with marine polyunsaturated fatty acids for fatty acid composition in plasma and erythrocytes among men.

SCOPE: Limited information exists on how the relationship between dietary intake of fat and fatty acids in erythrocytes and plasma is modulated by polymorphisms in the FADS gene cluster. We examined gene-diet interaction of total marine PUFA intake with a known gene encoding Δ-5 desaturase enzyme (FADS1) variant (rs174550) for fatty acids in erythrocyte membranes and plasma phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG). METHODS AND RESULTS: In this cross-sectional study, fatty acid compositions were measured using GC, and total intake of polyunsaturated fat from fish and fish oil was estimated using a food frequency questionnaire in a subsample (n = 962) of the Metabolic Syndrome in Men Study. We found nominally significant gene-diet interactions for eicosapentaenoic acid (EPA, 20:5n-3) in erythrocytes (pinteraction = 0.032) and for EPA in plasma PL (pinteraction = 0.062), CE (pinteraction = 0.035), and TG (pinteraction = 0.035), as well as for docosapentaenoic acid (22:5n-3) in PL (pinteraction = 0.007). After excluding omega-3 supplement users, we found a significant gene-diet interaction for EPA in erythrocytes (pinteraction < 0.003). In a separate cohort of the Kuopio Obesity Surgery Study, the same locus was strongly associated with hepatic mRNA expression of FADS1 (p = 1.5 × 10(-10) ). CONCLUSION: FADS1 variants may modulate the relationship between marine fatty acid intake and circulating levels of long-chain omega-3 fatty acids.

Longitudinal associations of serum fatty acid composition with type 2 diabetes risk and markers of insulin secretion and sensitivity in the Finnish Diabetes Prevention Study.

PURPOSE: To examine the longitudinal associations of serum fatty acid composition with type 2 diabetes, insulin secretion and insulin sensitivity over several years. METHODS: We conducted a prospective cohort study derived from the randomized Finnish Diabetes Prevention Study. Total serum fatty acid composition was measured using gas chromatography in 407 overweight, middle-aged people with impaired glucose tolerance at baseline (1993-1998) and annually during the intervention period (1994-2000). Longitudinal associations of 20 fatty acids and three desaturase activities (Δ5 (20:4n-6/20:3n-6, D5D), Δ6 (18:3n-6/18:2n-6, D6D), stearoyl-CoA desaturase-1 (16:1n-7/16:0, SCD-1)) with type 2 diabetes incidence, and estimates of insulin sensitivity (Matsuda), secretion (ratio of insulin and glucose concentrations) and ß-cell function (disposition index) by an oral glucose tolerance test were analyzed using Cox regression and linear mixed models. We validated estimated D5D and D6D using a known FADS1 gene variant, rs174550. RESULTS: The baseline proportions of 20:5n-3, 22:5n-3 and 22:6n-3, and D5D were associated with lower incidence of type 2 diabetes during a median follow-up of 11 years (HR per 1SD: 0.72, 0.74, 0.73, 0.78, respectively, P ≤ 0.01). These long-chain omega-3 fatty acids and D5D were associated with higher insulin sensitivity in subsequent years but not with disposition index. Saturated, monounsaturated and trans fatty acids and 18:3n-3, 18:2n-6, SCD-1 and D6D were inconsistently associated with type 2 diabetes or related traits. CONCLUSIONS: Serum long-chain omega-3 fatty acids and D5D predicted lower type 2 diabetes incidence in people at a high risk of diabetes attending to an intervention study; a putative mechanism behind these associations was higher insulin sensitivity.

Effect of fatty and lean fish intake on lipoprotein subclasses in subjects with coronary heart disease: a controlled trial.

BACKGROUND: Fish oil intake reduces serum triglycerides; however, little is known about the effects of dietary fish intake on lipoprotein subclasses. OBJECTIVE: We aimed at assessing the effect of fatty and lean fish intake on the lipoprotein subclasses in an intervention study. METHODS: The intervention study included 33 patients with coronary heart disease, who were aged 61.0 ± 5.8 (mean ± SD) years. The subjects were randomly assigned to a fatty fish (n = 11), lean fish (n = 12), or control (n = 10) diet for 8 weeks. Fish diets included at least 4 fish meals per week. Subjects in the control group consumed lean beef, pork, and chicken. Lipoprotein subclasses and their lipid components were determined by nuclear magnetic resonance spectroscopy. RESULTS: Concentrations of n-3 fatty acids and docosahexaenoic acid increased in the fatty fish group. The concentrations of cholesterol, cholesterol esters, and total lipids in very large high-density lipoproteins (HDLs) increased in the fatty fish group (overall difference P = .005, P = .002, and P = .007, respectively; false discovery rate P = .04, P = .04, and P = .05, respectively). The mean size of HDL particles increased in the fatty fish group (9.8 ± 0.3 nm at baseline and 9.9 ± 0.4 nm at end of study; overall difference P = .004, false discovery rate P = .04). The fish diets did not affect very-low-density lipoprotein or low-density lipoprotein size. CONCLUSION: Fatty fish intake at least 4 times per week increases HDL particle size which might have beneficial effect in patients with coronary heart disease.

Brain electrical activity during food presentation in obese binge-eating women.

Binge-eating (BE) subjects have shown altered brain activity at frontal regions during food presentation. The aim of this study was to examine the frontal brain electrical activity in obese BE women (n = 12) and in obese women without BE (non-BE, n = 13). Brain electrical activity was measured using a quantitative electroencephalography during a resting state (eyes-closed) and when the subjects focused (eyes-open) their attention on a picture of a landscape (control experiment) or on a meal (food experiment). The BE showed greater frontal beta activity (14-20 Hz) than the non-BE in both the eyes-closed (on average 52%) and the eyes-open situations and independently of the stimulus (control experiment: 57% and food experiment: 71%). No significant differences between the groups were found in alpha, delta or theta amplitudes. Increased beta activity correlated positively with the disinhibition factor of the Three-Factor Eating Questionnaire. Thus, our results suggest that elevated frontal beta activity may be a marker of dysfunctional disinhibition-inhibition mechanism, which could make the obese BE women more vulnerable or sensitive to food and the environmental cues.

Viscosity of oat bran-enriched beverages influences gastrointestinal hormonal responses in healthy humans.

Viscous fibers, including beta-glucan in oat bran, favorably affect satiety as well as postprandial carbohydrate and lipid metabolism. However, effects of fiber viscosity on modulation of satiety-related gut hormone responses are largely unknown. We examined the effects of modified oat bran, with or without its natural viscosity, on sensations of appetite and satiety-related gastrointestinal (GI) hormone responses to establish the relevance of viscosity of beta-glucan in oat bran. Twenty healthy, normal-weight participants (16 female, 4 male, aged 22.6 +/- 0.7 y) ingested 2 isocaloric (1250 kJ) 300-mL oat bran beverages with low or high viscosity (carbohydrates, 57.9 g; protein, 7.8 g; fat, 3.3 g; fiber, 10.2 g) after a 12-h fast in randomized order. Viscosity of the low-viscosity oat bran beverage was reduced by beta-glucanase treatment. Blood samples were drawn before and 15, 30, 45, 60, 90, 120, and 180 min after beverage consumption. The oat bran beverage with low viscosity induced a greater postprandial increase in satiety (P = 0.048) and plasma glucose (P < 0.001), insulin (P = 0.008), cholecystokinin (P = 0.035), glucagon-like peptide 1 (P = 0.037), and peptide YY (P = 0.051) and a greater decrease in postprandial ghrelin (P = 0.009) than the beverage with high-viscosity oat bran. Gastric emptying as measured by paracetamol absorption was also faster (P = 0.034) after low-viscosity oat bran beverage consumption. In conclusion, viscosity differences in oat beta-glucan in a liquid meal with identical chemical composition strongly influenced not only glucose and insulin responses, but also short-term gut hormone responses, implying the importance of food structure in the modulation of postprandial satiety-related physiology.

Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications.

BACKGROUND: Intake of fish and long-chain n-3 fatty acids has been of wide interest due to their beneficial effects on cardiovascular risk factors and lower coronary heart disease (CHD) risk. AIM OF THE STUDY: The aim of this pilot study was to examine the effects of fatty fish and lean (white) fish on fatty acid composition of serum lipids and cardiovascular risk factors in subjects with CHD using multiple drugs for this condition. METHODS: The study was an 8-week controlled, parallel intervention. Inclusion criteria were myocardial infarction or unstable ischemic attack, age under 70 years, use of betablockers and presence of sinus rhythm. The subjects were randomized to one of the following groups: 4 meals/week fatty fish (n = 11), 4 meals/week lean fish (n = 12) and control diet including lean meat (n = 10). RESULTS: The mean (+/-SD) of reported fish meals per week was 4.3 +/- 0.4, 4.7 +/- 1.1 and 0.6 +/- 0.4 in the groups, respectively. The proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids increased in the fatty fish group only (P < 0.05). Systolic and diastolic blood pressure levels decreased in the lean fish group (0 vs. 8 week: 3.5 +/- 3.2 and 4.6 +/- 3.6%, respectively, P < 0.05). Serum total triglyceride concentration did not significantly change. HDL cholesterol concentration change differed among groups but without significant post hoc differences. Apolipoprotein A-1 concentration decreased in the control group (0 vs. 8 week, P < 0.05). Coagulation factors, 25-hydroxy vitamin D, and heart rate variability (24 h Holter) did not change among the groups. CONCLUSIONS: Our results suggest that intake of lean fish at least four times per week could reduce blood pressure levels in CHD patients.

The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study.

BACKGROUND AND AIMS: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity. METHODS AND RESULTS: Altogether 151 healthy subjects (age 49+/-8 years, BMI 26.5+/-3.0kg/m(2)) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P=0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P=0.007 among three genotypes). The rare -250A allele was related to low HL activity (P<0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes. CONCLUSION: The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype.

Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors.

BACKGROUND: Both hempseed oil (HO) and flaxseed oil (FO) contain high amounts of essential fatty acids (FAs); i.e. linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), but almost in opposite ratios. An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes. It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile. AIM OF THE STUDY: To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids, plasma glucose and insulin, and haemostatic factors in healthy humans. METHODS: Fourteen healthy volunteers participated in the study. A randomised, double-blind crossover design was used. The volunteers consumed HO and FO (30 ml/day) for 4 weeks each. The periods were separated by a 4-week washout period. RESULTS: The HO period resulted in higher proportions of both LA and gamma-linolenic acid in serum cholesteryl esters (CE) and triglycerides (TG) as compared with the FO period (P < 0.001), whereas the FO period resulted in a higher proportion of ALA in both serum CE and TG as compared with the HO period (P < 0.001). The proportion of arachidonic acid in CE was lower after the FO period than after the HO period (P < 0.05). The HO period resulted in a lower total-to-HDL cholesterol ratio compared with the FO period (P = 0.065). No significant differences were found between the periods in measured values of fasting serum total or lipoprotein lipids, plasma glucose, insulin or hemostatic factors. CONCLUSIONS: The effects of HO and FO on the profile of serum lipids differed significantly, with only minor effects on concentrations of fasting serum total or lipoprotein lipids, and no significant changes in concentrations of plasma glucose or insulin or in haemostatic factors.

Antibodies against oxidized LDL and cardiolipin and mortality in patients with coronary heart disease.

The association between antibodies against oxidized LDL (oxLDL) and cardiolipin and the risks of death and cardiovascular disease events were evaluated in patients with established coronary heart disease (CHD). The patients (mean age: 61 years, range: 33-74 years) were participants in the EUROASPIRE study; 108 of them had undergone coronary artery bypass surgery, 106 had balloon angioplasty, 101 had a diagnosis of acute myocardial infarction (AMI), and 98 acute myocardial ischemia. Antibodies against oxLDL and cardiolipin were measured and incidence of CHD events and deaths were followed up for 5 years in 284 men and 129 women. During the follow-up 36 patients died and 21 had AMI. After adjustment for cardiovascular disease risk factors the relative risks (RR [95% confidence interval]) of death were 1 (reference), 2.50 (0.97-6.49) and 2.21 (0.85-5.80) in increasing tertile categories of anti-oxLDL antibody titers, respectively (P for trend 0.16). The risks of CHD-death or AMI combined were 1 (reference), 2.61 (1.02-6.65) and 1.06 (0.37-3.03) in increasing tertile categories of anticardiolipin antibody titers, respectively (P for trend 0.03). In conclusion, the results suggest that antibodies against oxLDL and cardiolipin are not major predictors of risks of death and CHD events in patients with established CHD.

Leucine7 to proline7 polymorphism in prepro-NPY gene and femoral neck bone mineral density in postmenopausal women.

Neuropeptide Y (NPY) is a versatile neurotransmitter that has recently been shown to regulate bone metabolism in animal and in vitro studies. We studied the influence of leucine7-to-proline7 (Leu7/Pro7) polymorphism of the NPY signal peptide gene on bone mineral density (BMD) before and after a 5-year hormone replacement therapy (HRT) in 316 early postmenopausal women participating in a randomized controlled trial nested in the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The participants were randomized into two treatment groups: the HRT group (n = 146) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate and calcium lactate, 500 mg/day (equal to 93 mg Ca2+) alone or in combination with vitamin D3, 100-300 IU/day. The non-HRT group (n = 170) received calcium lactate, 500 mg alone or in combination with vitamin D3, 100-300 IU/day. BMDs of the lumbar spine (L2-4) and proximal femur were measured by using dual X-ray absorptiometry (DXA). The frequency of Leu7/Pro7 polymorphism was 15.2%. At baseline, there were no significant differences in the lumbar or femoral neck BMD between the subjects who had Leu7Pro7 polymorphism and the normal subjects. After 5 years, the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7% in the HRT group, whereas both BMDs were decreased by 4-5% in the non-HRT group. After 5 years, the femoral neck BMD was significantly lower in those with the wild-type NPY polymorphism than in those with Leu7/Pro7 polymorphism (P = 0.040) in the non-HRT group. In the HRT group, the changes in BMD were quite modest and not significantly modified by Leu7/Pro7 genotype. We conclude that the Leu7/Pro7 polymorphism in NPY signal gene may favorably affect femoral neck BMD in postmenopausal women.

n-3 Fatty acids and 5-y risks of death and cardiovascular disease events in patients with coronary artery disease.

BACKGROUND: Data on the association of n-3 fatty acid content in serum lipids with mortality in patients with coronary artery disease (CAD) are limited. OBJECTIVE: We hypothesized that a high proportion of n-3 fatty acids in serum lipids would be associated with reduced risks of death and coronary events in patients with established CAD. DESIGN: We measured dietary intakes via food records and the fatty acid composition of serum cholesteryl esters (CEs) in 285 men and 130 women with CAD (x age: 61 y; range: 33-74 y). The patients participating in the EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) study were followed up for 5 y. RESULTS: During the follow-up, 36 patients died, 21 had myocardial infarctions, and 12 had strokes. The relative risks (RRs) of death adjusted for cardiovascular disease risk factors for subjects in the highest tertile of fatty acids in CEs compared with those in the lowest tertile were 0.33 (95% CI: 0.11, 0.96) for alpha-linolenic acid, 0.33 (0.12, 0.93) for eicosapentaenoic acid, and 0.31 (0.11, 0.87) for docosahexaenoic acid (P for trend = 0.063, 0.056, and 0.026, respectively). A high proportion of eicosapentaenoic acid in CEs was associated with a low risk of CAD death. Compared with no consumption, consumption of fish tended to be associated with a lower risk of death [1-57 g/d, RR = 0.50 (0.20, 1.28); > 57 g/d, RR = 0.37 (0.14, 1.00); P for trend = 0.059]. CONCLUSION: High proportions of n-3 fatty acids in serum lipids are associated with a substantially reduced risk of death.

Effect of alpha-linolenic acid-rich Camelina sativa oil on serum fatty acid composition and serum lipids in hypercholesterolemic subjects.

Camelina sativa-derived oil (camelina oil) is a good source of alpha-linolenic acid. The proportion of alpha-linolenic acid in serum fatty acids is associated with the risk of cardiovascular diseases. We studied the effects of camelina oil on serum lipids and on the fatty acid composition of total lipids in comparison to rapeseed and olive oils in a parallel, double-blind setting. Sixty-eight hypercholesterolemic subjects aged 28 to 65 years were randomly assigned after a 2-week pretrial period to 1 of 3 oil groups: camelina oil, olive oil, and rapeseed oil. Subjects consumed daily 30 g (actual intake, approximately 33 mL) of test oils for 6 weeks. In the camelina group, the proportion of alpha-linolenic acid in fatty acids of serum lipids was significantly higher (P <.001) compared to the 2 other oil groups at the end of the study: 2.5 times higher compared to the rapeseed oil group and 4 times higher compared to the olive oil group. Respectively the proportions of 2 metabolites of alpha-linolenic acid (eicosapentaenoic and docosapentaenoic acids) increased and differed significantly in the camelina group from those in other groups. During the intervention, the serum low-density lipoprotein (LDL) cholesterol concentration decreased significantly by 12.2% in the camelina oil group, 5.4% in the rapeseed oil group, and 7.7% in the olive oil group. In conclusion, camelina oil significantly elevated the proportions of alpha-linolenic acid and its metabolites in serum of mildly or moderately hypercholesterolemic subjects. Camelina oil's serum cholesterol-lowering effect was comparable to that of rapeseed and olive oils.

Association of the fatty acid profile of serum lipids with glucose and insulin metabolism during 2 fat-modified diets in subjects with impaired glucose tolerance.

BACKGROUND: Both the amount and quality of dietary fat can modify glucose and insulin metabolism. OBJECTIVE: The objective was to examine the relation between serum lipid fatty acids and glucose metabolism before and after the consumption of a diet enriched in either monounsaturated (Mono diet) or polyunsaturated (Poly diet) fatty acids. DESIGN: After consuming a high-saturated-fat run-in diet for 3 wk, 31 subjects with impaired glucose tolerance were randomly counseled to consume the Mono [40% fat; 11%, 19%, and 8% of energy as saturated, monounsaturated, and polyunsaturated fatty acids (S:M:P), respectively] or the Poly (34% fat; S:M:P of 11%:10%:10%) diet for 8 wk. Serum lipid fatty acids were measured, and an intravenous-glucose-tolerance test was performed at baseline and at 8 wk. RESULTS: At baseline, a higher glucose effectiveness (S(G)) was associated with higher proportions of oleic (r = 0.57, P = 0.04) and alpha-linolenic (r = 0.64, P = 0.01) acids in phospholipids. An increase in the proportions of oleic and alpha-linolenic acids in phospholipids was associated with a decrease in fasting plasma glucose [r = -0.53 (P = 0.002) and r = -0.47 (P = 0.009), respectively]. An increase in the S(G) was associated with an increase in the proportion of oleic acid (r = 0.55, P = 0.004) and with a decrease in that of arachidonic acid (r = -0.40, P = 0.04) in phospholipids. CONCLUSIONS: The beneficial changes in fasting plasma glucose and in the S(G) during the Mono diet were associated with alterations in the proportions of oleic, alpha-linolenic, and arachidonic acids in phospholipids.

Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study.

The association of the Pro12Ala polymorphism of the PPAR-gamma2 gene with the incidence of type 2 diabetes was investigated in 522 subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study. Subjects were randomized to either an intensive diet and exercise group or a control group. By 3 years of intervention, the odds ratio of the development of type 2 diabetes for subjects with the Ala12 allele was 2.11-fold compared with that for subjects with the Pro12Pro genotype (95% CI 1.20-3.72). The risk for type 2 diabetes increased also in subjects who gained weight or belonged to the control group. In the intervention group, subjects with the Ala12Ala genotype lost more weight during the follow-up than subjects with other genotypes (Pro12Pro vs. Ala12Ala P = 0.043), and none of subjects with the Ala12Ala genotype developed type 2 diabetes in this group. In conclusion, the Ala12 allele may predispose to the development of type 2 diabetes in obese subjects with IGT. However, beneficial changes in diet, increases in physical activity, and weight loss may reverse, to some extent, the diabetogenic impact of the Ala12 allele, possibly due to an improved insulin sensitivity.

Association of leucine 7 to proline 7 polymorphism in the preproneuropeptide Y with serum lipids in patients with coronary heart disease.

Leucine 7 (Leu7) to proline 7 (Pro7) substitution in the neuropeptide Y (NPY) gene has been associated with higher serum total and low-density lipoprotein (LDL) cholesterol levels, particularly in obese subjects. We investigated the frequency of the Pro7 allele and the association of the polymorphism with serum lipid levels in patients with coronary heart disease (CHD). A total of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross-sectional EUROASPIRE study. Of the subjects 39% used lipid-lowering drugs. The frequency of the Pro7 allele in CHD patients (0.082) did not differ from that in control subjects (0.071). The mean (+/-SD) serum total cholesterol concentration was higher in women with the Pro7 allele (7.57 +/- 0.57 mmol/L, n = 8) than in women with the Leu7Leu genotype (6.69 +/- 1.01 mmol/L, n = 69, P = 0.019), when subjects using lipid-lowering medication were excluded. In contrast, serum total cholesterol concentration did not significantly differ between the genotypes in men. The Leu7Pro polymorphism was not associated with serum LDL, high-density lipoprotein (HDL) cholesterol, and triglyceride concentrations. In conclusion, the Pro7 allele in the NPY gene was associated with higher serum total cholesterol concentration only in women with CHD who did not use lipid-lowering drugs.