Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study

Aims/hypothesis. The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. Methods. The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. Results. Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10 %, p = 0.03) but did not change on the monounsaturated fatty acid diet ( + 2 %, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E %). Here, insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet ( + 4.1 %, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (–5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12 % (p < 0.001). Conclusions/interpretation. A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E %). [Diabetologia (2001) 44: 312–319] Received: 21 August 2000 and in revised form: 8 November 2000     

Non-esterified fatty acids regulate lipid and glucose oxidation and glycogen synthesis in healthy man

Summary We examined the interrelationship of lipid and glucose metabolism in the basal state and during insulin stimulus in 19 healthy men (27±2 years, body mass index 23.6±0.6 kg/m²). In each subject, we performed a 4-h euglycaemic (5.3±0.1 mmol/l) hyperinsulinaemic (647±21 pmol/l) insulin clamp with indirect calorimetry in the basal state and during insulin infusion, and muscle biopsies before and at the end of the clamp. In the basal state, serum non-esterified fatty acid levels correlated directly with lipid oxidation (r =0.56, p<0.05) and indirectly with glucose oxidation (r = –0.80, p<0.001). Lipid and glucose oxidation rates were inversely related in the basal state (r = –0.47, p<0.05) and during insulin infusion (r = –0.65, p<0.01). Basal lipid oxidation and glycogen synthase total activity correlated inversely (r = –0.54, p<0.05). Lipid oxidation both in the basal state (r = –0.61, p<0.01) and during insulin infusion (r = –0.62, p<0.05) was inversely related to muscle glycogen content after the insulin clamp. Fasting plasma triglyceride concentration correlated directly to fasting insulin (r =0.55, p<0.05) and C-peptide (r =0.50, p<0.03) concentrations and inversely to non-oxidative glucose disposal rate at the end of clamp (r = –0.54, p<0.05). In conclusion: 1) Serum non-esterified fatty acid concentration enhances lipid and reduces glucose oxidation. 2) Lipid oxidation is inversely related to total glycogen synthase activity. 3) Lipid oxidation both in the basal state and during insulin stimulus correlates inversely with muscle glycogen content after insulin infusion. 4) Even in normotriglyceridaemic subjects, plasma triglycerides reduce insulin-stimulated non-oxidative glucose disposal. These data suggest that serum non-esterified fatty acids in physiologic concentrations have an important role in the regulation of lipid and glucose oxidation as well as glucose storage as glycogen. [Diabetologia (1994) 37: 202–209] Received: 2 June 1993 and in revised form: 27 August 1993     

Dietary fatty acids and insulin resistance

High-fat diets have been associated with insulin resistance, a risk factor for both Type II diabetes and heart disease. The effect of dietary fat on insulin varies depending on the type of fatty acid consumed. Saturated fatty acids have been consistently associated with insulin resistance. On the other hand, medium and long-chain fatty acid intakes are associated with insulin sensitivity, as are high intakes of ϕ3 fatty acids. Trans fatty acids appear to potentiate insulin secretion, at least in the short-term, to a greater degree than cis fatty acids. This may reflect chronic alterations in insulin sensitivity, although this remains to be tested. In summary, although it must be emphasized that all diets high in fat cause insulin resistance relative to high-carbohydrate diets, it appears that dietary saturated, short-chain and ϕ6 fatty acids have the most deleterious effects on insulin action.     

Effect of the Mediterranean diet on fasting concentrations of activated factor VII in healthy persons

INTRODUCTION AND OBJECTIVES: Many clinical and epidemiologic studies suggest that activated factor VII may be involved in the pathogenesis of coronary heart disease. Our objective was to determine the effect of a Mediterranean diet on plasma levels of activated factor VII in comparison to a low-fat diet and a diet rich in saturated fat. PATIENTS AND METHOD: The study population comprised 16 healthy normolipemic men who consumed 3 different diets in consecutive 28-day periods. The first diet was rich in saturated fat (38% calories as fat, 20% saturated fat), the second was a low-fat, high-carbohydrate diet (28% calories as fat, 10% saturated fat), and the third was enriched in monounsaturated fatty acids (38% calories as fat, 22% monounsaturated fat). At the end of each period, plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, total triglycerides, apolipoprotein A-I, apolipoprotein B, and glucose were measured. Activated factor VII was determined with a coagulation assay. RESULTS: The diet rich in saturated fat was associated with a significant increase in total cholesterol, LDL cholesterol, apolipoprotein AI, and apolipoprotein B in comparison to the other 2 diets. There were no significant differences between the carbohydrate-rich diet and the Mediterranean diet in any of the lipid parameters. The Mediterranean diet decreased plasma levels of factor VIIa in comparison to the diet rich in saturated fat (34.6+/-15.3 mU/mL vs 101.5+/-19.2 mU/mL; P<.05). CONCLUSIONS: In comparison to the diet rich in saturated fat or the high-carbohydrates diet, the Mediterranean diet decreased plasma concentrations of activated factor VII in healthy young men. This phenomenon may constitute another protective mechanism of the Mediterranean diet in reducing cardiovascular risk.     

Hepatic lipid metabolism in severe human obesity

The rate of incorporation of glycerolcarbon into triglyceride (TG) in liver slices obtained from 17 severely obese normolipoproteinemic patients during jejunoileal bypass was significantly elevated compared to normal controls. The obese patients had an almost sevenfold increase in hepatic TG content as well. None of the patients had manifest diabetes, though increased basal levels of insulin and impaired glucose tolerance during oral glucose tolerance tests (OGTT) were common. There were statistically significant positive Spearman rank correlations between plasma insulin levels and TG synthesis (r = 0.57; p < 0.01), TG content (r = 0.54; p < 0.01), and serum fatty acids (r = 0.52; p < 0.05). The basal insulin levels were also positively correlated to the incorporation rate of fructose-carbon into fatty acids (r = 0.47; p < 0.05). The sum of insulin values during OGTT showed a trend toward positive correlation with the hepatic cholesterol content (r = 0.34; p < 0.10). The hepatic protein content as well as the rate of leucinecarbon incorporation into proteins did not differ from controls. However, there was a trend toward a negative correlation between protein synthesis and basal plasma insulin levels (r = ?0.33; p < 0.10). It is suggested that liver steatosis in severely obese patients is due to significantly increased hepatic lipid synthesis in the face of elevated levels of serum fatty acids. The possible importance of plasma insulin is also emphasized.     

A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome

Objective

Dietary changes are major factor in determining cardiovascular risk. We assessed the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (MetS) from the LIPGENE project.

Methods and design

Clinical intervention study: the patients (n = 337) were randomly assigned to one of four diets for 12 weeks each: two high fat diets, one rich in saturated fat (HSFA) and the other rich in monounsaturated fat (HMUFA), and two low fat diets, one high in complex carbohydrates (LFHCC) supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) and the other LFHCC diet with placebo (LFHCC). Measurements: the effects on MetS risk criteria were recorded before and after the intervention period.

Results

An enlarged waist circumference (≥88 cm for women and ≥102 cm for men) was present among 95% of the participants, 88% had elevated blood pressure (>130/85 mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (≥5.55 mmol/L), 51% were hypertriacylglycerolemic (≥1.7 mmol/L), and 72% had low HDL cholesterol (<1.0 mmol/L for men, and <1.3 mmol/L for women). The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (p < 0.05). Thus the prevalence of MetS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (p < 0.028).

Conclusions

The consumption of a low-fat high-carbohydrate supplemented with n-3 diet reduced the risk of MetS as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets.     

Divergent responses of serum lipoproteins to changes in dietary carbohydrate and cholesterol in cynomolgus monkeys

The metabolic effects of dietary carbohydrates (simple versus complex) on lipogenesis, glucose, and insulin responses are well known, but information is lacking on the effect of carbohydrate types on different serum lipoprotein fractions. We therefore studied the differences in responses of serum lipids, lipoproteins, apoproteins, and plasma glucose and insulin to changes in dietary carbohydrates and cholesterol in 12 male cynomolgus monkeys (Macaca fascicularis). For 6 weeks, each monkey was fed one of four semipurified, high-carbohydrate (76.5% cal) diets that provided sucrose or starch with and without 1 mg/kcal cholesterol. Sucrose diet without added cholesterol resulted in consistently higher serum total cholesterol than with a similar starch diet. In contrast, cholesterol-enriched starch diet caused marked increase in serum total cholesterol when compared to similar sucrose diet. Neither starch nor sucrose diets elicited a VLDL-triglyceride response. Observations on apoB, VLDL- and LDL-cholesterol levels essentially reflected serum total cholesterol changes by diet. Changes in HDL-subfractions to dietary carbohydrates were seen mainly in HDL₂, with starch producing lower values than sucrose (p < 0.01). Among the four diets, cholesterol, triglyceride and phospholipid contents of HDL₂, as well as apoA-I and apoA-II contents of serum total lipoproteins were lowest with cholesterol-enriched starch diet feeding. High cholesterol diets increased the cholesterol to triglyceride ratios of LDL, irrespective of type of carbohydrate (p < 0.01), whereas the ratios of cholesterol to phospholipids showed significant carbohydrate effect (starch > sucrose) and cholesterol effect for HDL₂. Neither plasma glucose nor insulin showed any diet-related differences. Thus, a high level of dietary carbohydrate with and without added cholesterol provoked divergent responses of serum lipids and lipoproteins between sucrose and starch. Although reasons for the paradoxical responses are not readily apparent, the experiment provides a useful model for further metabolic studies.     

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.     

A low-carbohydrate/high-fat diet improves glucoregulation in type 2 diabetes mellitus by reducing postabsorptive glycogenolysis

The aim of this study was to examine the mechanisms by which dietary carbohydrate and fat modulate fasting glycemia. We compared the effects of an eucaloric high-carbohydrate (89% carbohydrate) and high-fat (89% fat) diet on fasting glucose metabolism and insulin sensitivity in seven obese patients with type 2 diabetes using stable isotopes and euglycemic hyperinsulinemic clamps. At basal insulin levels glucose concentrations were 148 +/- 11 and 123 +/- 11 mg/dl (8.2 +/- 0.6 and 6.8 +/- 0.6 mmol/liter) on the high-carbohydrate and high-fat diet, respectively (P < 0.001), with insulin concentrations of 12 +/- 2 and 10 +/- 1 microIU/ml (82 +/- 11 and 66 +/- 10 pmol/liter) (P = 0.08). Glucose production was higher on the high-carbohydrate diet (1.88 +/- 0.06 vs. 1.55 +/- 0.05 mg/kg.min (10.44 +/- 0.33 vs. 8.61 +/- 0.28 micromol/kg.min) (P < 0.001) because of higher glycogenolysis. Gluconeogenic rates were not different between the diets. During the use of hyperinsulinemic euglycemic clamps, insulin-mediated suppression of glucose production and stimulation of glucose disposal were not different between the diets. Free fatty concentrations were suppressed by 89 and 62% (P < 0.0001) on the high-carbohydrate and high-fat diet, respectively. We conclude that short-term variations in dietary carbohydrate to fat ratios affect basal glucose metabolism in people with type 2 diabetes merely through modulation of the rate of glycogenolysis, without affecting insulin sensitivity of glucose metabolism.     

Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity,insulin resistance,glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets

Aims/hypothesis Gastric inhibitory polypeptide (GIP) receptor antagonism with (Pro³)GIP improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure/function in ob/ob mice. This study examined the ability of (Pro³)GIP to counter the development of obesity, insulin resistance and diabetes in mice fed high-fat and cafeteria diets. Materials and methods Young Swiss TO mice on standard chow or high-fat, cafeteria or high-carbohydrate diets received daily injections of either saline or (Pro³)GIP (25 nmol kg^-1day^-1) over 16 weeks. Food intake, body weight, and circulating glucose and insulin were measured frequently. At 16 weeks, glucose tolerance, insulin sensitivity, HbA_1c, circulating hormones and plasma lipids were assessed. Adipose tissue, liver and muscle were excised and weighed, and their histology and triacylglycerol content were further examined. Results (Pro³)GIP significantly reduced body weight, enhanced locomotor activity, and improved HbA_1c, glucose tolerance, beta cell responsiveness and insulin sensitivity in mice fed high-fat and cafeteria diets (p < 0.05 to p < 0.01). Similarly, (Pro³)GIP significantly reduced plasma corticosterone and triacylglycerols (p < 0.05 to p < 0.001), while glucagon, resistin and adiponectin were unchanged. (Pro³)GIP decreased adipose tissue mass (p < 0.01) and the triacylglycerol content of liver, muscle and adipose tissue (p < 0.01 to p < 0.001). Adipocyte size and liver morphology were partially normalised. (Pro³)GIP did not significantly affect any of these parameters in mice fed a high-carbohydrate diet. Conclusions/interpretation (Pro³)GIP protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets. This highlights chemical GIP receptor antagonism as a new possibility for the treatment of obesity and associated metabolic disturbances.     

Medium‐chain fatty acids ameliorate insulin resistance caused by high‐fat diets in rats

Background High dietary intake of saturated fat impairs insulin sensitivity and lipid metabolism. The influence of fatty acid chain length, however, is not yet fully understood, but evidence exists for different effects of saturated long‐chain (LC) versus saturated medium‐chain (MC) fatty acids (FA). Methods To investigate the effects of the FA chain length, male Wistar rats were fed high‐fat diets containing triacylglycerols composed of either MC‐ or LCFA for 4 weeks; rats fed maintenance diet served as a control. The animals underwent euglycemic hyperinsulinemic clamping or oral metabolic tolerance testing respectively; enzyme activities of mitochondrial (EC2.3.1.21 carnitine palmitoyl transferase) and peroxisomal (EC1.3.3.6 acyl‐CoA oxidase) FA oxidation were measured in liver and muscle. Results LCFA consumption resulted in higher fasted serum insulin and glucose concentrations compared to controls, while MCFA‐fed animals did not differ from controls. Insulin sensitivity was reduced by 30% in the LCFA group while the MCFA group did not differ from controls. Feeding MCFA resulted in the controls' lowered fasted and post‐prandial triacylglycerol concentration compared to LCFA, while triacylglycerol concentrations in muscle were higher in both high‐fat groups compared to controls. No diet‐induced changes were found in acyl‐CoA oxidase (ACO) activity (liver and muscle), while LCFA feeding significantly raised carnitine palmitoyltransferase activity. Conclusions The chain length of saturated fatty acids in isocaloric diets affects insulin sensitivity, lipid metabolism and mitochondrial fatty acid oxidation without influencing body weight. While dietary LCFA clearly impair insulin sensitivity and lipid metabolism, MCFA seem to protect from lipotoxicity and subsequent insulin resistance without caloric restriction. Copyright © 2009 John Wiley & Sons, Ltd.     

Relationship of dietary fat and serum cholesterol ester and phospholipid fatty acids to markers of insulin resistance in men and women with a range of glucose tolerance

High-fat diets are associated with insulin resistance, however, this effect may vary depending on the type of fat consumed. The purpose of this study was to determine the relationship between intakes of specific dietary fatty acids (assessed by 3-day diet records and fatty acid composition of serum cholesterol esters [CEs] and phospholipids [PLs]) and glucose and insulin concentrations during an oral glucose tolerance test (OGTT). Nineteen men and 19 women completed the study. Nine subjects had type 2 diabetes or impaired glucose tolerance. Fasting insulin correlated with reported intakes of total fat (r = .50, P < .01), monounsaturated fat (r = .44, P < .01), and saturated fat (r = .49, P < .01), but not with trans fatty acid intake (r = .11, not significant [NS]). Fasting glucose also correlated with total (r = .39, P < .05) and monounsaturated fat intakes (r = .37, P < .05). In multivariate analysis, both total and saturated fat intake were strong single predictors of fasting insulin (R2 approximately .25), and a model combining dietary and anthropometric measures accounted for 47% of the variance in fasting insulin. Significant relationships were observed between fasting insulin and the serum CE enrichments of myristic (C14:0), palmitoleic (C16:1), and dihomo-gamma-linolenic (C20:3n-6) acids. In multivariate analysis, a model containing CE 14:0 and percent body fat explained 45% of the variance in fasting insulin, and C14:0 and age explained 30% of the variance in fasting glucose. PL C20:3n-6 explained 30% of the variance in fasting insulin, and a model including PL C18:1n-11 cis, C20:3n-6, age and body fat had an R2 of .58. In conclusion, self-reported intake of saturated and monounsaturated fats, but not trans fatty acids, are associated with markers of insulin resistance. Furthermore, enhancement of dihomo-gamma-linolenic and myristic acids in serum CE and PL, presumably markers for dietary intake, predicted insulin resistance.     

Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients.

Fifteen patients with Type 2 diabetes were given two diets rich in either saturated fat or polyunsaturated fat in alternate order over two consecutive 3-week periods on a metabolic ward. Both diets contained the same amount of fat, protein, carbohydrates, dietary fibre, and cholesterol. The proportions of saturated, monounsaturated and polyunsaturated fatty acids in the saturated fat diet were 16, 10, and 5%-energy and in the polyunsaturated fat diet (PUFA) 9, 10, and 12%-energy. The PUFA diet contained a high proportion of n-3 fatty acids. Metabolic control improved significantly in both dietary periods, due to both qualitative dietary changes and a negative energy balance. The serum lipoprotein concentrations decreased on both diets but the serum lipids were significantly lower after the PUFA diet (serum triglycerides -20%, p = 0.001; serum cholesterol -5%, p = 0.03; VLDL-triglycerides -29%, p less than 0.001; and VLDL-cholesterol -31%, p = 0.001) than after the saturated fat diet. Average blood glucose concentrations during the third week were significantly higher fasting (+15%, p less than 0.01), and during the day at 1100 h (+18%, p less than 0.001) and 1500 h (+17%, p = 0.002) on PUFA than on the saturated fat diet. Significantly higher blood glucose levels were also recorded with a standard breakfast, while the sum of the insulin values was lower (-19%, p = 0.01). HbA1c did not differ significantly between the two dietary periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between Mediterranean Diet Score and atherothrombotic risk: Findings from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994

Background

Mediterranean diet has been promoted as the preferred dietary model for cardiovascular disease prevention in the United States.

Objective

We sought to evaluate the degree to which the Mediterranean diet is associated with reduced levels of atherothrombotic biomarkers in a population-based sample in the U.S.

Design

Data from 13,197 adults between the ages of 18 and 90 were collected and atherothrombotic risk factors assessed as part of the NHANES III, 1988–1994. Adherence to the Mediterranean diet was evaluated using food frequency questionnaires, supplemented by the 24-h dietary recall data, to develop Mediterranean Diet Scores (MedDietScore) that were analyzed in tertiles. The cross-sectional relationship of MedDietScore to atherothrombotic factors were analyzed using multiple variable regression analysis adjusted for complex sampling design using SUDAAN.

Results

The components of the Mediterranean diet and the dietary pattern's associations with atherothrombotic risk factors differed by age and gender. For men <45 years of age as MedDietScore increased: total cholesterol/HDL cholesterol (TC/HDL) ratio (p = 0.0390), serum insulin (p = 0.0414), and white blood cell (WBC) (p = 0.0246) decreased. For men ≥45 years as MedDietScore increased: TC/HDL ratio (p = 0.0008), Hemoglobin A1c (HgbA1c) (p = 0.0001), HOMA index (p = 0.0486), C-reactive protein (p = 0.0034), fibrinogen (p = 0.0028) decreased and HDL cholesterol (HDL-c) levels (p < 0.0001) increased. For pre-menopausal women, as MedDietScore increased: TC/HDL ratio (p < 0.0001), non-HDL cholesterol (p = 0.0012), apolipoprotein B (p = 0.0112), HgbA1c (p = 0.0001), decreased and HDL-c levels (p < 0.0001) increased. For post-menopausal women, as MedDietScore increased: TC/HDL ratio (p = 0.0005), Triglycerides (p < 0.0001), serum insulin (p = 0.0062), HOMA index (p = 0.0063) and Homocysteine (Hcy) (0.0046) levels decreased and HDL-c levels (p = 0.0005) increased.

Conclusions

Mediterranean diet appears to be associated with selective measures of cardioprotective lipid profiles, glucose metabolism, and inflammation and coagulation levels.     

Effects of lipid-lowering diets enriched with monounsaturated and polyunsaturated fatty acids on serum lipoprotein composition in patients with hyperlipoproteinaemia.

Controlled comparisons of the effects of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) as a part of lipid-lowering diets in persons with hyperlipoproteinaemia are sparse. The present study was carried out at a metabolic ward. Forty hyperlipidaemic patients (25 hypercholesterolaemic and 15 hypertriglyceridaemic) were given a 3-week diet rich in either MUFA (saturated fatty acids 7.3 energy% (E%), MUFA 14.6 E%, PUFA 4.8 E%) or PUFA (saturated fatty acids 7.8 E%, MUFA 8.4 E%, PUFA 10.4 E%), but otherwise with an identical composition. The mean serum cholesterol reduction on the MUFA diet was 12% (P < 0.001), with a low density lipoprotein cholesterol reduction of 11% (P < 0.001). The corresponding reductions on the PUFA diet were 15% (P < 0.001) and 16% (P < 0.001). The serum apolipoprotein B and A-I concentrations decreased highly significantly by 13% and 11% on the MUFA diet and by 14% and 11% on the PUFA diet. None of these changes differed between the two diets. Neither were there any differences between the diets regarding the effects on blood glucose, serum insulin and plasma fibrinogen, but there was a significant decrease in serum insulin with a significant reduction of the insulin/glucose ratio after the MUFA diet. The results of this study indicate that MUFA and PUFA are interchangeable within the given frames in lipid lowering diets even in patients with hyperlipidaemia.     

Postprandial oxidative stress is modulated by dietary fat in adipose tissue from elderly people

We have investigated whether dietary fat modifies the postprandial oxidative stress in adipose tissue of elderly people. Twenty participants received three diets for 4 weeks each: SFA-rich diet, Mediterranean (Med) diet enriched in MUFA with virgin olive oil, and a low-fat, high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid from plant origin) (CHO-PUFA diet). After 12 h of fasting, volunteers received a breakfast reflecting the fatty acid composition of the diet ingested in the preceding dietary period. Med diet induced higher postprandial SOD2 and TrxR mRNA levels, and CHO-PUFA diet induced higher GPx1 and TrxR mRNA levels compared with SFA-rich diet. Med and CHO-PUFA breakfasts induced a postprandial increase in plasma reduced glutathione (GSH), and a greater postprandial GSH/oxidized glutathione ratio compared to the SFA-rich diet. Our study suggests that the consumption of Med and CHO-PUFA diets may reduce postprandial oxidative stress compared to an SFA-rich diet, which may be due to higher antioxidant enzymes gene expression in adipose tissue.     

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 comparative reductions of the plasma lipids and lipoproteins by dietary polyunsaturated fats: Salmon oil versus vegetable oils

The lower plasma lipid levels and lower incidence of atherosclerotic diseases in Greenland Eskimos suggested that the unusual fatty acids present in their diet of seal and fish may be anti-atherogenic. These fatty acids are eicosapentaenoic (C20:5) and docosahexaenoic (C22:6) acids and are of the omega-3 fatty acid family. We have compared a salmon oil diet containing high levels of these unique fatty acids to a control diet high in saturated fat and to a vegetable oil diet high in linoleic acid (C18:2). All diets contained 40% of the total calories as fat and 500 mg of cholesterol; they differed only in fatty acid composition. In 4 wk the salmon oil diet reduced plasma cholesterol levels from 188 to 162 mg/dl (p < 0.001) and triglyceride levels from 77 to 48 mg/dl (p < 0.005). LDL and VLDL cholesterol levels changed from 128 to 108 and 13 to 8 mg/dl (p < 0.005), respectively. HDL cholesterol levels did not change. The vegetable oil diet caused similar decreases in cholesterol levels but did not lower triglyceride levels. The omega-3 fatty acids comprised up to 30% of the total fatty acids in each plasma lipid class after the salmon diet. Fish oils contain fatty acids which may be metabolically unique and potentially useful in the control of both hypercholesterolemia and hypertriglyceridemia.     

Dietary fatty acid composition during pregnancy and lactation in the rat programs growth and glucose metabolism in the offspring

AIMS/HYPOTHESIS: We investigated of the effects of fatty acid composition of the maternal diet on fetal and postnatal growth, morphology of the pancreas and glucose metabolism and muscle hexosamine concentrations in the adult offspring of rats. METHODS: High-fat diets enriched with either saturated or unsaturated fatty acids were fed to female adult rats 2 weeks before mating until the end of the weaning period. After weaning, the offspring was maintained on a diet with a balanced fatty acid content. At 3 months of age, pancreatic Langerhans islet size and number were assessed by morphometric analysis and oral glucose tolerance tests (OGTT) were carried out. RESULTS: The unsaturated fatty acid diet showed lower birth weight and reduced postnatal weight gain. Furthermore, this group showed increased pancreatic islet numbers without affected glucose tolerance at the age of 12 weeks. The offspring of the saturated fatty acid diet group showed a reduced number of large pancreatic islets. Moreover, a faster and higher insulin response was observed after an oral glucose load in these animals. Muscle hexosamine concentrations were not different between groups. CONCLUSION/INTERPRETATION: Maternal diets enriched with either saturated fatty acids or unsaturated fatty acids had opposite effects on pancreatic islet development in rat offspring, with consequences for the insulin response at 12 weeks of age. Therefore, maternal dietary fatty acid composition plays a role in programming growth, pancreatic development and glucose metabolism in the offspring.