Apolipoprotein E enrichment of immuno-separated chylomicron and chylomicron remnants following saturated fatty acids

AimWe examined the effect of meal fatty acids on lipid and apolipoprotein concentrations of very low density lipoprotein (VLDL) and chylomicron/chylomicron remnants in lipid fractions with a Svedberg flotation rate (S_f) 60–400 and S_f 20–60.Methods and resultsSix healthy middle-aged men received in random order mixed meals enriched with saturated (SFA), polyunsaturated (PUFA) or monounsaturated (MUFA) fatty acids on 3 occasions. VLDL and chylomicron/chylomicron remnants in the lipid fractions were separated by immunoaffinity chromatography against apo B-100. In the S_f 60–400 chylomicron/chylomicron remnants, triacylglycerol and cholesterol concentrations were significantly lower following PUFA compared with SFA and MUFA (P ≤ 0.05). Apolipoprotein (apo) E responses were significantly higher after SFA in chylomicron/chylomicron remnants and VLDL compared with PUFA and MUFA (P < 0.007). However, apo B responses (particle number) were higher following MUFA than SFA (P = 0.039 for chylomicron/chylomicron remnants). Composition of the chylomicron/chylomicron remnants (expressed per particle) revealed differences in their triacylglycerol and apo E contents; in the S_f 60–400 fraction, SFA-rich chylomicron/chylomicron remnants contained significantly more triacylglycerol than MUFA (P = 0.028), more apo E than PUFA- and MUFA-rich particles (P < 0.05) and in the S_f 20–60 fraction, more apo E than MUFA (P = 0.009).ConclusionThere are specific differences in the composition of chylomicron/chylomicron remnants formed after saturated compared with unsaturated fatty acid-rich meals which could determine their metabolic fate in the circulation and subsequent atherogenicity.     

Olive, soybean and palm oils intake have a similar acute detrimental effect over the endothelial function in healthy young subjects

Background and aimCurrently, more than 30% of the caloric intake in the Colombian population comes from vegetable oil consumption mainly by the ingestion of deep-fried foods. Recently, it has been reported that unsaturated fatty acid rich oils have a beneficial effect on the endothelial function. Nevertheless, it is well know that the deep-frying process alters the chemical composition of vegetable oils and can produce adverse effects in the endothelial function.ObjectiveTo evaluate the acute effect of the ingestion of large amounts of olive, soybean and palm oils, fresh and at two different deep-fry levels, on the glucose and lipid profiles and the endothelial function.Methods and resultsTen healthy young volunteers were included in the study. After performing a baseline evaluation of cardiovascular risk factors and drawing a fasting blood sample, subjects were exposed to a randomly assigned potato soup meal containing 60 mL of one of three different vegetable oils (olive, soybean and palm), either fresh or at one of two different deep-fry levels (10 and 20 fries, respectively). Flow-mediated vasodilation (FMD) was performed in fasting conditions and 3 h after the intake of the oil rich meal. Furthermore, blood samples were taken at these stages for the lipid profiles and plasma glucose determinations. All the meals resulted in a similar acute endothelial impairment (FMD decrease of 32.1%, confidence interval [CI] 95%, 28.0–36.2) and postprandial increase in triglycerides (27.03%, CI 95%, 20.5–33.3), independently of the type of oil ingested (p = 0.44) and regardless of its deep-fry level (p = 0.62). No correlation was found between endothelial impairment and postprandial triglyceride increment (r = −0.22, p = 0.09).ConclusionsNo difference was found in the acute adverse effect of the ingestion of different vegetable oils on the endothelial function. All the vegetable oils, fresh and deep-fried, produced an increase in the triglyceride plasma levels in healthy subjects.     

Consumption of diets with different type of fat influences triacylglycerols-rich lipoproteins particle number and size during the postprandial state

Background and aims

Previous evidence suggests that dietary fat could influence the composition and size of triacylglycerols-rich lipoproteins (TRL). In a controlled intervention study on healthy subjects, we evaluated the influence of 3 dietary interventions, with different types of fat on postprandial TRL particle size and number.

Methods and results

Volunteers followed three different diets for four weeks each, according to a randomized crossover design. Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); high CHO enriched with ALNA diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After a 12-h fast, volunteers consumed a breakfast with 1 g fat and 7 mg cholesterol per kg body weight and a fat composition similar to that consumed in each of the diets: Butter meal: 35% SFA; Olive oil meal: 36% MUFA; Walnut meal: 16% PUFA, 4% α-linolenic acid. Tryglicerides (TG) in TRL (large and small TRL) were determined by ultracentrifugation and size and number of lipoprotein particles were measured with Nuclear Magnetic Resonance Spectroscopy at different time points. The olive oil meal reduced the number of total TRL postprandial particles compared with the other meals (P = 0.002). Moreover, the olive oil meal also increased the TRL particle size compared with the walnut meal (P = 0.001).

Conclusion

Our data showed that short-term intake of the Mediterranean diet and the acute intake of an olive oil meal lead to the formation of a reduced number and higher-size TRL particle compared with other fat sources. These novel findings have implications for understanding the postprandial lipoprotein mechanisms, and could favour the lower cardiovascular risk in Mediterranean countries.     

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 aimsHepatic 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 resultsAltogether 151 healthy subjects (age 49 ± 8 years, BMI 26.5 ± 3.0 kg/m²) 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 (3.6 g 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.ConclusionThe 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 soybean D-LeciVita product on serum lipids and fatty acid composition in type 2 diabetic patients with hyperlipidemia

Background and aimHyperlipidemia is one of the major risk factors of cardiovascular complication in diabetes. High intake of soy product has been suggested to prevent cardiovascular disease. The purpose of this study was to evaluate if dietary supplement of soybean D-LeciVita product, rich in polyunsaturated phospholipids (with 12% lecithin, 35% soy protein) affects serum lipids and serum and erythrocyte phospholipid fatty acid composition in type 2 diabetic patients.Methods and resultsForty-seven patients (men and post-menopausal women) with isolated hypertriglyceridemia (IHTG) and combined hyperlipidemia (CHL), aged 43–70 years, were given 15 g of D-LeciVita powder as a water suspension in a single evening dose during the follow-up period of 12 weeks. Patients kept their diabetic diet relatively constant. Treatment was associated with a significant (p ≤ 0.001) decrease in serum total cholesterol and triglyceride levels by 12% and 22%, respectively. LDL-cholesterol decreased by 16% and HDL-cholesterol increased by 11% (p ≤ 0.001). Our study shows a 27% decrease in LDL-cholesterol (p ≤ 0.001) and a 12% increase in HDL-cholesterol (p ≤ 0.01) in CHL type 2 diabetic patients. Triglyceride levels decreased in type 2 diabetic patients with IHTG and CHL by 29% and 13%, respectively (p ≤ 0.01 and p ≤ 0.05). Our results show decrease in SFA and increase in n-6 and n-3 PUFA in serum and erythrocyte phospholipids. SFA decreased and n-3 PUFA increased in serum and erythrocyte phospholipids in IHTG and CHL groups.ConclusionThe present study indicated that added to a regular diet, soybean D-LeciVita product (combination of soy protein and lecithin) is associated not only with lipid-lowering effects but also with more favorable serum phospholipids fatty acid profile in type 2 diabetic patients with hyperlipidemia.     

Functionality of postprandial larger HDL2 particles is enhanced following CETP inhibition therapy

ObjectiveTo evaluate the impact of CETP inhibition on the capacity of individual postprandial HDL subspecies to promote key steps of the reverse cholesterol transport pathway.MethodsThe capacity of HDL particles to mediate cellular free cholesterol efflux and selective hepatic uptake of cholesteryl esters was evaluated throughout postprandial phase (0–8 h) following consumption of a standardised mixed meal before and after treatment for 6 weeks with atorvastatin alone (10 mg/d) and subsequently with combination torcetrapib/atorvastatin (60/10 mg/d) in 16 patients displaying low HDL-C levels (<40 mg/dl).ResultsThe larger HDL2b and HDL2a subfraction displayed a superior capacity to mediate cellular free cholesterol efflux via both SR-BI and ABCG1-dependent pathways than smaller HDL3 subspecies. CETP inhibition specifically enhanced the capacity of HDL2b subfraction for both SR-BI and ABCG1 dependent efflux. However, only the SR-BI-dependent efflux to HDL2b subspecies can be further enhanced during postprandial lipemia following CETP inhibition. Concomitantly, postprandial lipemia was associated with a reduced capacity of total HDL particles to deliver cholesteryl esters to hepatic cells in a drug independent manner.ConclusionCETP inhibition specifically improves postprandial SR-BI and ABCG1-dependent efflux to larger HDL2b subspecies. In addition, CETP inhibition improves HDL-CE delivery to hepatic cells and maintains an efficient direct return of cholesteryl esters to the liver during postprandial lipemia.     

Acute effects of casein on postprandial lipemia and incretin responses in type 2 diabetic subjects

Background and aimsExaggerated and prolonged postprandial lipemia is potentially atherogenic and associated with type 2 diabetes. Limited data exist regarding the influence of dietary protein on postprandial lipemia in type 2 diabetes. We investigated, over 8-h, the acute effects of casein alone or in combination with carbohydrate on postprandial lipid and incretin responses to a fat-rich meal in type 2 diabetes.Methods and resultsEleven type 2 diabetic subjects ingested four test meals in random order: an energy-free soup plus 80 g of fat (control-meal); control-meal plus 45 g carbohydrates (CHO-meal); control-meal plus 45 g of casein (PRO-meal); and PRO-meal plus 45 g carbohydrates (CHO + PRO-meal). Triglyceride and retinyl palmitate responses were measured in plasma and in a chylomicron-rich and chylomicron-poor fraction. We found no significant differences in triglyceride responses to PRO- and CHO + PRO-meal compared to the control-meal. However, the addition of casein to the CHO-meal reduced the raised triglyceride response in the chylomicron-rich fraction. Retinyl palmitate responses did not differ significantly between meals in the chylomicron-rich fraction, whereas the PRO-meal increased retinyl palmitate in the chylomicron-poor fraction. PRO- and PRO + CHO-meal increased insulin and glucagon compared to the control-meal. PRO + CHO-meal increased the glucose-dependent insulinotropic peptide response while no change in glucagon-like peptide-1 responses was detected.ConclusionsThe data presented suggest that casein per se did not modulate the postprandial triglyceride response in type 2 diabetes. When added to carbohydrate, casein suppressed the triglyceride response in the chylomicron-rich fraction, increased insulin and glucagon but did not affect the incretin responses.     

A sequential two meal challenge reveals abnormalities in postprandial TAG but not glucose in men with increasing numbers of metabolic syndrome components

ObjectiveTo examine the impact of increasing numbers of metabolic syndrome (MetS) components on postprandial lipaemia.MethodsHealthy men (n = 112) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0 min) and lunch (330 min). Lipids, glucose and insulin were measured in the fasting sample, with triacylglycerol (TAG), non-esterified fatty acids and glucose analysed in the postprandial samples.ResultsSubjects were grouped according to the number of MetS components regardless of the combinations of components (0/1, 2, 3 and 4/5). As expected, there was a trend for an increase in body mass index, blood pressure, fasting TAG, glucose and insulin, and a decrease in fasting high-density lipoprotein cholesterol with increasing numbers of MetS components (P ≤ 0.0004). A similar trend was observed for the summary measures of the postprandial TAG and glucose responses. For TAG, the area under the curve (AUC) and maximum concentration (max C) were significantly greater in men with ≥3 than <3 components (P < 0.001), whereas incremental AUC was greater in those with 3 than 0/1 and 2, and 4/5 compared with 2 components (P < 0.04). For glucose, max C after the test breakfast (0–330 min) and total AUC (0–480 min) were higher in men with ≥3 than <3 components (P ≤ 0.001).ConclusionsOur data analysis has revealed a linear trend between increasing numbers of MetS components and magnitude (AUC) of the postprandial TAG and glucose responses. Furthermore, the two meal challenge discriminated a worsening of postprandial lipaemic control in subjects with ≥3 MetS components.     

Improvement of the omega 3 index of healthy subjects does not alter the effects of dietary saturated fats or n-6PUFA on LDL profiles

Background and AimsDietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated.MethodsIn a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA.ResultsThe diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (− 8%, p = 0.013) and LDL cholesterol (LDL-C) level (− 8%, p = 0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency.ConclusionImprovement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles.     

Consuming a balanced high fat diet for 16 weeks improves body composition,inflammation and vascular function parameters in obese premenopausal women

ObjectiveInflammation, insulin resistance and vascular dysfunction characterize obesity and predict development of cardiovascular disease (CVD). Although women experience CVD events at an older age, vascular dysfunction is evident 10 years prior to coronary artery disease. Questions remain whether replacing SFA entirely with MUFA or PUFA is the optimal approach for cardiometabolic benefits. This study tested the hypotheses that: a) body composition, inflammation and vascular function would improve with a high fat diet (HFD) when type of fat is balanced as 1/3 SFA, 1/3 MUFA and 1/3 PUFA; and b) body composition, inflammation and vascular function would improve more when balanced HFD is supplemented with 18C fatty acids, in proportion to the degree of 18C unsaturation.MethodsObese premenopausal women were stabilized on balanced HFD and randomized to consume 9 g/d of encapsulated stearate (18:0), oleate (18:1), linoleate (18:2) or placebo.ResultsSignificant improvements occurred in fat oxidation rate (↑6%), body composition (%fat: ↓2.5 ± 2.1%; %lean: ↑2.5 ± 2.1%), inflammation (↓ IL-1α, IL-1β, 1 L-12, Il-17, IFNγ, TNFα, TNFβ) and vascular function (↓BP, ↓PAI-1, ↑tPA activity). When compared to HFD + placebo, HFD + stearate had the greatest effect on reducing IFNγ (↓74%) and HFD + linoleate had the greatest effect on reducing PAI-1 (↓31%).ConclusionsBalancing the type of dietary fat consumed (SFA/MUFA/PUFA) is a feasible strategy to positively affect markers of CVD risk. Moreover, reductions in inflammatory molecules involved in vascular function might be enhanced when intake of certain 18C fatty acids is supplemented. Long term effects need to be determined for this approach.     

Postprandial hyperlipidemia in overt and subclinical hypothyroidism

Background and aimsLipid alterations in overt hypothyroidsm (OH) were well known, but its changes in subclinical hypothyroidism (SCH) and postprandial period were not clear. The aim of this study is to evaluate postprandial lipemia by oral lipid tolerance test (OLTT) in patients with OH and SCH.Materials and methodologyTwenty-five OH and 27 SCH, totally 52 hypothyroid patients [mean age 38.3 ± 12.8 year, body mass index (BMI): 29.0 ± 5.8 kg/m²] and 23 BMI- and age-matched healthy controls (mean age 36.7 ± 11.9 years; BMI: 27.1 ± 6.9 kg/m²) were included to the study. Anthropometric measurements and HOMA-IR levels were measured. Basal and postprandial lipid profile at 2nd, 4th, 6th and 8th hours were determined by oral lipid tolerance test.ResultsThere were not any statistical differences among three groups (control, OH and SCH) in terms of mean fasting levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglyceride. On the contrary, mean triglyceride levels at postprandial 8th hour in both OH and SCH patients were higher than control subjects (p = 0.017 and p = 0.049, respectively). Again mean postprandial 8th hour VLDL-cholesterol levels in OH group were also higher than control subjects (p = 0.05). In addition mean HOMA-IR value of SCH and OH patients was similar with control subjects (1.5 ± 1.4 in OH; 1.3 ± 0.8 in SCH; 2.2 ± 2.2 in control group).ConclusionsAlthough total, LDL and VLDL-cholesterol, and triglyceride levels were not different from healthy controls, triglyceride and/or VLDL-cholesterol levels apparently increased with OLTT in both OH and SCH patients. Decreased lipid clearance may be responsible for this result.     

Postprandial chylomicrons and adipose tissue lipoprotein lipase are altered in type 2 diabetes independently of obesity and whole-body insulin resistance

Background and aimsPostprandial lipoprotein abnormalities in type 2 diabetes are associated with insulin resistance. The role of other diabetes-related factors is still not clear. The aim of this study is to differentiate the effects of whole-body insulin resistance, obesity, and type 2 diabetes on postprandial dyslipidaemia and lipoprotein lipase (LPL) in adipose tissue.Methods and resultsTen subjects with obesity and diabetes (OD), 11 with obesity alone (O), and 11 normal-weight controls (C) – males, aged 26–59 years, with fasting normo-triglyceridaemia underwent measurements of cholesterol, triglycerides, apo B-48 and apo B-100 concentrations in plasma lipoproteins separated by density gradient ultracentrifugation before and after a fat-rich meal. Fasting and postprandial (6 h) LPL activity was determined in abdominal subcutaneous adipose tissue biopsy samples. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp. OD and O subjects had similar degrees of adiposity (BMI, waist circumference, fat mass) and insulin resistance (insulin stimulated glucose disposal and M/I). They also showed a similarly higher postprandial increase in large VLDL lipids (triglyceride incremental AUC 188 ± 28 and 135 ± 22 mg/dl·6 h) than C (87 ± 13 mg/dl·6 h, M ± SEM, p < 0.05). OD had an increased chylomicron response compared to O (triglyceride incremental AUC 132 ± 23 vs. 75 ± 14 mg/dl·6 h, p < 0.05). OD had significantly lower fasting and postprandial adipose tissue heparin-releasable LPL activity than O and C.ConclusionsIn insulin-resistant conditions of obesity, with and without diabetes, large VLDL are increased after a fat-rich meal. In addition, diabetic patients compared to obese subjects have an increased postprandial chylomicron response and a reduced adipose tissue LPL activity.     

Dietary fatty acids and peripheral artery disease in adults

BackgroundPeripheral artery disease (PAD) is a debilitating condition involving atherosclerosis. Although saturated, monounsaturated and polyunsaturated fatty acids have strong associations with atherosclerosis, it is unclear if diets high in these fatty acids affect PAD.MethodsWe studied 6352 adults aged 40 years and older who participated in the U.S. National Health and Nutrition Examination Survey between 1999 and 2004. Ankle brachial index (ABI) was assessed by standardized blood pressure measurements, and we defined PAD as an ABI < 0.9. Fatty acid intake was assessed by validated 24-h dietary recall. We used multivariable linear and logistic regression to estimate associations between intakes of dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MFAs), marine omega-3 fatty acids (N-3), linolenic acid (LNA), and omega-6 fatty acids (N-6) and ABI/PAD.ResultsThe prevalence and 95% confidence interval (CI) of PAD was 5.2% (95% CI 4.6–5.8).There were no associations between ABI and intakes of marine N-3 (p = 0.83) or N-6 (p = 0.19) in adjusted models. In contrast, LNA was associated with higher ABI (p = 0.04) and SFA tended to be associated with lower ABI (p = 0.06) in adjusted models. In addition, higher SFA was associated with a higher prevalence of PAD: adjusted odds ratio 1.30 (95% CI 1.01–1.67; p = 0.04) and a trend toward slower gait speed (p = 0.08).ConclusionIn this nationally representative sample, higher dietary intakes of LNA and SFAs were associated with higher and lower ABI, respectively. Prospective studies are needed to confirm the potential protective effects of dietary LNA and detrimental effects of dietary SFAs on PAD.     

Acute exercise improves postprandial cardiovascular risk factors in overweight and obese individuals

ObjectivesThe effects of 30 min of exercise on postprandial lipaemia in the overweight and obese are unknown as previous studies have only investigated bouts of at least 60 min in lean, healthy individuals. The aim of this study was to investigate whether a single 30-min bout of resistance, aerobic or combined exercise at moderate-intensity would decrease postprandial lipaemia, glucose and insulin levels as well as increase resting energy expenditure and increase fat oxidation following a high fat meal consumed 14 h after the exercise bout, in overweight and obese individuals compared to no exercise. We also compared the effects of the different exercise modalities.MethodsThis study was a randomized cross-over design which examined the postprandial effects of 30 min of different types of exercise in the evening prior to a breakfast meal in overweight and obese men and women. Participants were randomized on four occasions, each one-week apart, to each condition; either no exercise, aerobic exercise, resistance exercise or a combination of aerobic exercise and resistance exercise.ResultsAn acute bout of combination training did not have any significant effect on postprandial measurements compared to no exercise. However, aerobic exercise significantly reduced postprandial triglyceride levels by 8% compared to no exercise (p = 0.02) and resistance exercise decreased postprandial insulin levels by 30% compared to aerobic exercise (p = 0.01).ConclusionThese results indicate that a single moderate-intensity 30 min bout of aerobic or resistance exercise improves risk factors associated with cardiovascular disease in overweight and obese individuals.     

Calcium and vitamin D modulate postprandial vascular function: A pilot dose–response study

BackgroundCalcium and vitamin D may modulate postprandial endothelial function.Subjects and MethodsSeven lean, young males completed a single blind randomized crossover design where they consumed three breakfast meals containing varying calcium and vitamin D (meal 1 ～200 mg/15 IU, meal 2 ～450 mg/140 IU, and meal 3 ～700 mg/265 IU). Stiffness index (SI), reflective index (RI) and pulse rate (PR) were serially assessed from the digital volume pulse by photoplethysmography (Pulse Trace PT-1000, Micro Medical, UK).ResultsIncremental areas under the curve over 3 h (Δ) were analyzed by repeated measures ANOVA. ΔPTH was significantly less suppressed with meal A than with meal B and C (P = 0.003). In contrast, ΔRI was significantly more suppressed following meal A than with either meal B or C (P = 0.021). ΔSI did not change with meal ingestion and there was no difference in the rise of Δglucose, Δinsulin and ΔPR between meals.ConclusionHigher calcium and vitamin D at breakfast prevented the fall in postprandial vascular tone without changes in glucose or insulin.     

Effect of postprandial lipemia on plasma concentrations of A-FABP,RBP-4 and visfatin

Background and aimsSeveral studies indicate that changes in the plasma concentrations of adipocyte-fatty acid binding protein (A-FABP), retinol binding protein-4 (RBP-4) and visfatin are associated with chronic states of insulin resistance. Recent studies have shown that postprandial lipemia induces an acute state of insulin resistance. The aim of this study was to investigate the effect of postprandial lipemia on the plasma concentrations of A-FABP, RBP-4 and visfatin.Methods and resultsIn a within-subject crossover study, we administered a standardized high-fat meal to 24 healthy subjects (12 males and 12 females). Plasma concentrations of adipocytokines were measured in the morning after an overnight fast and during postprandial lipemia, i.e. 2, 4 and 6 hours after meal ingestion (postprandial experiment). To exclude potential confounding factors affecting the adipocytokine plasma concentrations, a control experiment without meal ingestion was performed over the same time period (postabsorptive control experiment). Comparing plasma concentrations of A-FABP, RBP-4 and visfatin between the postprandial and the postabsorptive control experiments, we found no significant differences. Within either of the two experiments, a decrease of A-FABP was noted reaching, however, statistical significance only in the postprandial experiment, i.e. 2 and 4 hours after meal ingestion.ConclusionPostprandial lipemia has no significant effect on the plasma concentrations of visfatin, A-FABP or RBP-4 in relation to their postabsorptive plasma profiles. We conclude that prolonged states of insulin resistance are required to affect plasma concentrations of these adipocytokines.     

ADAM17_i33708A > G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the Genetics of Lipid Lowering Drugs and Diet Network study

Background and aimsThe disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A > G, i14121C > A, i33708A > G, i48827A > C, i53440C > T, and i62781 G > T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA).Methods and resultsADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A > G polymorphism exhibited significantly higher risk of obesity (P = 0.003), were shorter (P = 0.017), had higher insulin (P = 0.016), and lower HDL-C concentrations (P = 0.027) than AA subjects. For the ADAM17_i33708A > G SNP, homozygotes for the A allele displayed higher risk of obesity (P = 0.001), were heavier (P = 0.011), had higher BMI (P = 0.005), and higher waist measurements (P = 0.023) than GG subjects. A significant gene-diet interaction was found (P = 0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P < 0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P > 0.5)ConclusionThese findings support that ADAM17 (m1254A > G and i33708A > G) SNPs may contribute to obesity risk. For the ADAM17_i33708A > G SNP, this risk may be further modulated by (n-6) PUFA intake.     

Postprandial modulation of serum paraoxonase activity and concentration in diabetic and non-diabetic subjects

ObjectivesTo analyse the HDL associated anti-oxidant enzyme paraoxonase-1, during postprandial hyperlipaemia.Methods and resultsType 2 diabetic patients (n = 72), glucose intolerant patients (n = 10) and controls (n = 38) consumed a high fat:high carbohydrate meal. Blood samples were collected up to 4 h and analysed for lipids and paraoxonase-1. In vitro studies examined HDL function with respect to the enzyme. There were significant postprandial increases in serum triglycerides. Paraoxonase-1 activity decreased significantly throughout the postprandial phase. Concentrations of the enzyme initially decreased significantly, but returned to fasting concentrations at 4 h. Specific activities were significantly lower at 4 h, compared to fasting. The decrease in specific activity was linked to the dynamic phase of postprandial lipoprotein metabolism. Apo AI limited loss of paraoxonase-1. HDL isolated after being subjected to postprandial conditions in vitro had reduced capacity to associate with and stabilise PON1.ConclusionsPostprandial hyperlipaemia was associated with changes to serum paraoxonase-1, consistent with a reduced anti-oxidant potential of HDL. No differences were observed between diabetic and non-diabetic patients, suggesting that the effect was linked to postprandial hyperlipaemia. Modifications to paraoxonase-1 could contribute to increased risk of vascular disease associated with postprandial lipaemia, particularly in diabetic patients, who are already deficient in serum paraoxonase-1.     

Extended-release Niacin Acutely Suppresses Postprandial Triglyceridemia

ObjectivePostprandial triglyceridemia predicts cardiovascular events. Niacin might lower postprandial triglycerides by restricting free fatty acids. Immediate-release niacin reduced postprandial triglycerides, but extended-release niacin failed to do so when dosed the night before a fat challenge. The study aims were to determine whether extended-release niacin dosed before a fat challenge suppresses postprandial triglycerides and whether postprandial triglycerides are related to free fatty acid restriction.MethodsA double-blinded, placebo-controlled, random-order crossover experiment was performed, in which healthy volunteers took 2 g extended-release niacin or placebo 1 hour before heavy cream. We sampled blood over 12 hours and report triglycerides and free fatty acid as means ± standard deviation for incremental area under the curve (AUC) and nadir.ResultsBy combining 43 fat challenges from 22 subjects, postprandial triglycerides incremental AUC was +312 ± 200 mg/dL*h on placebo versus +199 ± 200 mg/dL*h on extended-release niacin (33% decrease, P = .02). The incremental nadir for free fatty acid was ?0.07 ± 0.15 mmol/L on placebo versus ?0.27 ± 0.13 mmol/L on extended-release niacin (P < .0001), and free fatty acid incremental AUC decreased from +2.9 ± 1.5 mmol/L*h to +1.5 ± 1.5 mmol/L*h on extended-release niacin (20% decrease, P = .0015). The incremental AUC for triglycerides was strongly related to the post-dose decrease in free fatty acid (r = +0.58, P = .0007).ConclusionsGiven right before a fat meal, even a single dose of extended-release niacin suppresses postprandial triglyceridemia. This establishes that postprandial triglycerides suppression is an acute pharmacodynamic effect of extended-release niacin, probably the result of marked free fatty acid restriction. Further study is warranted to determine whether mealtime dosing would augment the clinical efficacy of extended-release niacin therapy.     

Effect of two fasting periods of different duration on ghrelin response to a mixed meal

Background and aimThe inhibitory effect of food on ghrelin secretion is reduced in several eating disorders such as restricting type anorexia nervosa, bulimia and obesity. These conditions are frequently characterised by irregular distribution of meals during the day. It is unknown whether two short fasting periods different duration affect ghrelin response to a mixed meal. Aim of the present study was to examine, in healthy volunteers, the effects of two fasting periods of different duration on pre- and post-prandial ghrelin concentrations after a standard mixed meal.Methods and resultsNine healthy men (mean age ± S.E.M., 25.1 ± 0.2 years; mean body mass index ± S.E.M., 22.6 ± 0.3 kg/m²) were studied in 2 days after 12 h of fasting (12F) and 17 h of fasting (17F) with a within-subject repeated measure design. On both days they ate a standardized mixed meal. Before each meal hunger rating was evaluated with a visual analogue score. Blood samples for ghrelin, insulin, and glucose were collected at 0, 45, 60, 90, 120, 150 and 180 min after meal.Comparing fasting values of 17F with 12F there was a significant increase in plasma ghrelin (160 ± 20 vs. 146 ± 18 fmol/mL, P = 0.015) and hunger rating (evaluated with a visual analogue scores) (7.0 ± 0.3 vs. 5.1 ± 0.4, P < 0.003). A positive correlation between fasting ghrelin and hunger rating (r = 0.52, P < 0.01) was found. Circulating ghrelin decreased after both meals without any significant difference in relation with the previous length of fasting. Also postmeal ghrelin AUC as well as fasting and postmeal concentrations of insulin and glucose were similar after 12F and 17F.ConclusionsIn healthy subjects a longer fasting period increases ghrelin concentration but did not affect post-prandial ghrelin response to a mixed meal.