Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome.

Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering high-density lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.

A monounsaturated fatty acid-rich diet reduces macrophage uptake of plasma oxidised low-density lipoprotein in healthy young men.

During atherogenesis, a pathological accumulation of lipids occurs within aortic intimal macrophages through uptake of plasma oxidised LDL (oxLDL). The aim of the present study was to determine whether macrophage uptake of plasma oxLDL and LDL susceptibility to oxidation may be determined by quantity and quality of dietary fat. Twenty healthy young men were subjected to three dietary periods, each lasting 4 weeks. The first was an SFA-enriched diet (38 % fat, 20 % SFA), which was followed by a carbohydrate (CHO)-rich diet (30 % fat, < 10 % SFA, 55 % CHO) or a MUFA olive oil-rich diet (38 % fat, 22 % MUFA) following a randomised cross-over design. After each diet period, LDL particles were oxidised with Cu ions to determine LDL susceptibility to oxidation and subsequently incubated with the U937-macrophage cell line to determine the percentage of uptake of plasma oxLDL. The shift from the MUFA diet to the SFA- or CHO-rich diets reduced the resistance of LDL particles to oxidation, decreasing lag time (P = 0.038) and increasing the propagation rate (P = 0.001). Furthermore, the MUFA-rich diet demonstrated reduced macrophage uptake of plasma oxLDL (P = 0.031) as compared with the SFA-rich diet. Finally, macrophage uptake of plasma oxLDL was correlated (r 0.45; P = 0.040) with total amount of conjugated dienes after LDL oxidation. Our data suggest that a MUFA-rich diet may have favourable effects on cardiovascular risk since it prevents the oxidative modifications of LDL and reduces macrophage uptake of plasma oxLDL.

Factor VII polymorphisms influence the plasma response to diets with different fat content, in a healthy Caucasian population.

UNLABELLED: To determine the influence of the factor VII gene polymorphisms, R353Q and 5'F7, on factor VII Ag plasma levels after the consumption of diets with different fat contents. METHODS: 59 healthy individuals (42 RR, 16 RQ, 1 QQ at the R353Q and 46 A1A1, 13 A1A2 at the 5'F7) consumed 3 diets during 4-weeks each: a Saturated diet (SAT) enriched in saturated fatty acid (SFA) (38% fat, 20% SFA), followed by a carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a Mediterranean diet (MEDIT) enriched in monounsaturated fatty acid (MUFA) (38% fat, 22% MUFA) following a randomized crossover design. Plasma lipids and FVII Ag plasma levels were determined at the end of each dietary period. RESULTS: After a SAT diet, RR homozygotes had greater concentrations of FVII Ag compared with MEDIT and CHO diets than did carriers of the minority Q allele (82.76 +/- 1.3 vs. 75.02 +/- 2.4, p = 0.001). The 5'F7 polymorphism behaved in a similar fashion (A1A1 81.98 +/- 1.4 vs. A1A2 75.37 +/- 2.4, p = 0.026). CONCLUSIONS: Our data show that carriers of the RR and/or A1A1 genotype present higher FVII Ag levels after the consumption of a SAT diet compared with the MEDIT and CHO rich diets.

Postprandial lipemia is modified by the presence of the APOB-516C/T polymorphism in a healthy Caucasian population.

Apolipoprotein (apoB) plays a fundamental role in the transport and metabolism of plasma triacylglycerols (TAGs) and cholesterol. Several apoB polymorphic sites have been studied for their potential use as markers for coronary heart disease in the population. In view of the importance of apoB in postprandial metabolism, our objective was to determine whether the presence of the -516C/T polymorphism in the APOB gene promoter could influence postprandial lipoprotein metabolism in healthy subjects. Forty-seven volunteers who were homozygous for the E3 allele at the APOE gene were selected (30 homozygous for the common genotype (C/C) and 17 heterozygotes for the -516T allele (C/T). They were given a fat-rich meal containing 1 g fat and 7 mg cholesterol per kg body weight and vitamin A 60,000 IU/m(2) body surface. Fat accounted for 60% of calories, and protein and carbohydrates for 15 and 25% of energy, respectively. Blood samples were taken at time 0, every 1 h until 6 h, and every 2.5 h until 11 h. Total cholesterol and TAGs in plasma, and cholesterol, TAGs and retinyl palmitate in triacylglycerol-rich lipoproteins (large and small triacylglycerol-rich lipoproteins) were determined by ultracentrifugation. Individuals carrying the C/T genotype presented greater postprandial concentrations of TAGs in small triacylglycerol-rich lipoproteins than did carriers of the C/C genotype (P = 0.022). Moreover, C/T individuals presented higher concentrations of plasma TAGs during the postprandial period than did C/C subjects (P = 0.039). No other statistically significant genotype-related differences for other parameters were observed. These results suggest that the presence of the genotype C/T is associated with a higher postprandial response. Thus, the allele variability in the -516C/T polymorphism in the APOB gene promoter may partly explain the interindividual differences in postprandial lipemic response in healthy subjects.

The APOB -516C/T polymorphism has no effect on lipid and apolipoprotein response following changes in dietary fat intake in a healthy population.

Our goal was to determine whether the presence of the -516C/T polymorphism in the APOB gene promoter modifies the lipid response to changes in the amount and quality of dietary fat. We studied 97 young healthy volunteers (70 males and 27 females), 62 homozygotes for the -516C allele (C/C) (47 males and 15 females), 34 heterozygotes for the -516T allele (C/T) (22 males and 12 females) and one male homozygote for the -516T allele (T/T). Subjects consumed three different diets in successive 4-week dietary periods. During the first 28 days, all subjects consumed a saturated fatty acid (SFA)-rich diet (38% fat and 20% SFA). Then, using a randomized crossover design, subjects were assigned a carbohydrate (CHO)-rich diet (30% fat and 55% carbohydrate) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat and 22% MUFA). At the end of each dietary period, plasma concentrations of triacylglycerols and of total, LDL, and HDL cholesterol were measured. No differences in plasma lipid and apolipoprotein response were found after changes in dietary fat intake in relation to the -516C/T polymorphism in our study population. In conclusion, our data suggest that the APOB -516C/T polymorphism has no effect on the lipid profile after changes in dietary fat intake in a healthy population.

The apolipoprotein E gene promoter (-219G/T) polymorphism determines insulin sensitivity in response to dietary fat in healthy young adults.

Insulin sensitivity (IS) is determined by genetic and environmental factors, including diet. The apoE gene promoter -219G/T polymorphism is associated with coronary heart disease and increased postprandial triacylglycerol-rich lipoprotein concentration, circumstances related to insulin resistance. Thus, our aim was to determine whether this polymorphism modified the IS response to dietary fat in healthy young adults. Volunteers (n = 43) with the apoE3/E3 genotype (8 GG, 25 GT and 10 TT) completed 3 dietary periods, each lasting 4 wk. They first consumed a SFA-rich diet [38% fat (% of energy in the total diet), 20% SFA (% of energy in the total diet)], and then, in a randomized, crossover design, a carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat, 22% MUFA). After each diet period, we investigated peripheral IS using the insulin suppression test. The steady-state plasma glucose (SSPG) concentration was lower (P < 0.05) in GG subjects than in GT and TT individuals, regardless of the diet consumed. Significant diet x genotype interactions were found for SSPG and plasma nonesterified FFA (NEFA) concentrations. Thus, the shift from the SFA-rich diet to the MUFA- or CHO-rich diets decreased (P < 0.05) the SSPG and NEFA concentrations in GG and GT, but not in TT subjects. In conclusion, carriers of the -219T allele are less insulin sensitive than GG individuals. Furthermore, only carriers of the -219G allele have improved IS when MUFA- or CHO-rich diets are consumed instead of a SFA-rich diet.

The Ala54Thr polymorphism of the fatty acid-binding protein 2 gene is associated with a change in insulin sensitivity after a change in the type of dietary fat.

BACKGROUND: Insulin resistance, a condition associated with type 2 diabetes, results from the interaction of environmental and genetic factors. OBJECTIVE: We examined the influence of the intestinal fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism on insulin sensitivity. DESIGN: Fifty-nine healthy young subjects (28 were Ala54/Ala54, 27 were Ala54/Thr54, and 4 were Thr54/Thr54) completed 3 diets, each of which lasted 4 wk. The first diet, which all subjects consumed, was a high-saturated fatty acid (SFA) diet (38% of energy as fat and 20% of energy as SFAs). The second and third diets were administered according to a randomized crossover design, and they consisted of a low-fat and high-carbohydrate diet (CHO diet; 28% of energy from fat and <10% of energy from SFAs) and a high-monounsaturated fatty acid (MUFA) diet (called the Mediterranean diet; 38% of energy from fat and 22% of energy from MUFAs). All food and drinks were prepared and provided in the research kitchen. We determined in vivo insulin resistance by using the insulin suppression test with somatostatin. RESULTS: Steady state plasma glucose concentrations were significantly higher in Ala54Thr subjects after the SFA diet than after the CHO diet or the Mediterranean diet. The plasma free fatty acid concentrations in these subjects were significantly lower after the CHO and Mediterranean diets than after the SFA diet. However, no significant differences between the 3 diets were observed in the Ala54 allele homozygotes. CONCLUSION: Insulin sensitivity decreased in subjects with the Thr54 allele of the FABP2 polymorphism when SFAs were replaced by MUFAs and carbohydrates.

The -514 C/T polymorphism in the hepatic lipase gene promoter is associated with insulin sensitivity in a healthy young population.

Impaired insulin action has been associated with diabetes, dyslipidemia and atherosclerotic vascular disease. The expression of insulin resistance results from the interaction of environmental and genetic factors. Human hepatic lipase (HL) is a lipolytic enzyme that plays a role in the metabolism of several lipoproteins, while insulin up-regulates the activity of HL via insulin-responsive elements in the HL promoter. We have examined the influence of -514 C/T polymorphism in the hepatic lipase gene promoter on insulin sensitivity in 59 healthy young subjects (30 males and 29 females). The volunteers were subjected to three dietary periods, each lasting four weeks. During the first period all subjects consumed a saturated fat (SFA)-enriched diet with 38% as fat (20% SFA, 12% monounsaturated fatty acids (MUFA) and 6% polyunsaturated fatty acids (PUFA)). In the second and third dietary periods, a randomized crossover design was used, consisting of a low fat, high carbohydrate diet (CHO diet) (< 10% SFA, 12% MUFA and 6% PUFA) and a high-MUFA, or Mediterranean diet, with < 10% SFA, 22% MUFA and 6% PUFA. We determined the in vivo insulin resistance using the insulin suppression test with somatostatin. Steady-state plasma glucose (SSPG) concentrations (a measure of insulin sensitivity) were significantly higher in men carriers of the -514T allele after the consumption of the SFA diet than after the CHO diet and the Mediterranean diet. This effect was not observed in women. Moreover, there were no significant differences in insulin sensitivity after the three diets in men and women with the CC genotype. In summary, our results show an improvement in insulin sensitivity in men with the -514T allele of the HL promoter polymorphism, when MUFA and carbohydrates are consumed instead of SFA fat.

The influence of the apolipoprotein E gene promoter (-219G/ T) polymorphism on postprandial lipoprotein metabolism in young normolipemic males.

The apolipoprotein E (apoE) gene promoter (-219G/T) polymorphism has been associated with increased risk of myocardial infarction, premature coronary heart disease, and decreased plasma apoE concentrations. We examined whether the -219G/T polymorphism could modify the postprandial response of triacylglycerol-rich lipoproteins (TRLs). Fifty-one healthy apoE 3/3 male volunteers (14GG, 29GT, and 8TT) were given a vitamin A fat-loading test consisting of 1 g of fat/kg body weight and 60,000 IU of vitamin A per m2 of body surface area. Blood samples were taken at time 0 and every hour until the sixth hour, and every 2 hours and 30 minutes until the eleventh hour. Cholesterol, triacylglycerols (TGs), and apoE were determined in plasma; and cholesterol, TG, apoB-100, apoB-48, and retinyl palmitate (RP) were analyzed in lipoprotein fractions. Postprandial lipemia data revealed that subjects with the -219TT genotype had a higher postprandial response of large TRL-cholesterol (P < 0.03), large TRL-triacylglycerols (P < 0.001), large TRL-RP (P < 0.004), and small TRL-apoB-48 (P < 0.03) than carriers of the -219G allele. Moreover, the -219TT subjects had the lowest postprandial levels of serum apoE (P < 0.05). In conclusion, the -219G/T polymorphism may influence TRL metabolism during the postprandial period, thus prolonging postprandial lipemia in subjects with the TT genotype.