Increased intake of fruits and vegetables in overweight subjects: effects on body weight, body composition, metabolic risk factors and dietary intake.

A diet rich in fruits and vegetables has been associated with several health benefits. However, the effects on body weight (BW) and metabolic markers are not fully known. The present study investigated the effects of increased intake of fruits and vegetables in overweight and obese men and women on dietary habits, anthropometry and metabolic control. In a 16-week controlled intervention, thirty-four men and thirty-four women aged 35-65 years (BMI>27 kg/m2) were randomised to an intervention (IN) or a reference (RG) group. All participants received general dietary advice, and subjects in the IN group received fruits and vegetables for free, of which ≥500 g had to be eaten daily. BW, waist circumference (WC), sagittal abdominal diameter (SAD), plasma insulin, blood glucose, glycated Hb (HbA1c), serum lipids, blood pressure, plasminogen activator inhibitor-1 activity, urinary isoprostane (iso-8-PGF 2α) and serum carotenoids were measured. Diet was assessed using 3-d weighed food records. In all, thirty subjects in the IN group and thirty-two in the RG group completed the intervention. Intake of fruits and vegetables doubled in the IN group, whereas intake of fruits increased in the RG group. Serum α- and ß-carotene concentrations and intakes of folate and vitamin C increased significantly in the IN group. Energy intake, BW, WC and SAD decreased significantly in both groups. Supine systolic blood pressure decreased significantly in the IN group, with no between-group differences. No significant changes were observed for other metabolic markers. Provision of fruits and vegetables led to substantially increased intakes, with subsequent favourable changes in anthropometry and insulin levels, which tended to be more pronounced in the IN group. The observed improvements may, in combination with improved nutritional markers, have health benefits in the long term.

Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study.

OBJECTIVE: Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF). METHODS: A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation. RESULTS: At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers. CONCLUSIONS: Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.

Serum fatty-acid composition and the risk of Alzheimer's disease: a longitudinal population-based study.

BACKGROUND/OBJECTIVES: It is unknown if a specific fatty-acid composition influences the development of Alzheimer's disease (AD). Nutrition is a possible target for prevention of dementia and especially omega-3-based fatty acids (n-3 FAs) have previously been suggested to be beneficial for cognition. The objective was to ascertain whether serum FAs predicts the risk of incident AD and dementia in a longitudinal population-based cohort. SUBJECTS/METHODS: Uppsala Longitudinal Study of Adult Men started in 1970. The proportions of FAs in serum cholesteryl esters were estimated in men (n=2009) who were 50 years old at baseline. During a 35 year follow-up time, 213 men had developed dementia, out of which 91 AD. The associations were analyzed with Cox proportional hazards and logistic regression; adjusted for age, education and vascular risk factors. RESULTS: Subjects with a higher proportion of saturated FAs had a decreased risk of AD in crude and multi-adjusted models (hazard ratio for 1-s.d. increase in palmitic acid 0.72; 95% confidence intervals: 0.59-0.89). These associations persisted even in the group of approximately 85-year-old survivors. n-3 FAs FAs were not associated with decreased risk of AD or dementia. CONCLUSIONS: In contrast to experimental studies, saturated FAs were inversely associated with risk of AD. No evidence of a protective effect of n-3 FAs against dementia was found. The results remained essentially unchanged if competing risk from mortality was taken into account.

Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women.

BACKGROUND AND AIMS: Two Amerindian populations--Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. METHODS AND RESULTS: Fasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women. CONCLUSIONS: The high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation.

Replacing dairy fat with rapeseed oil causes rapid improvement of hyperlipidaemia: a randomized controlled study.

BACKGROUND: Rapeseed oil (RO), also known as canola oil, principally contains the unsaturated fatty acids 18:1n-9, 18:2n-6 and 18:3n-3 and may promote cardiometabolic health. OBJECTIVE: To investigate the effects on lipoprotein profile, factors of coagulation and insulin sensitivity of replacing a diet rich in saturated fat from dairy foods (DF diet) with a diet including RO-based fat (RO diet). DESIGN: During a 2×3-week randomized, controlled, cross-over trial, 20 free-living hyperlipidaemic subjects were provided with isocaloric test diets that differed in fat composition alone. Blood lipoprotein profile, coagulation and fibrinolytic factors and insulin sensitivity (euglycaemic clamp) were determined before and after the dietary intervention. RESULTS: All subjects completed the study, and compliance was high according to changes in serum fatty acids. The RO diet, but not the DF diet, reduced the levels of serum cholesterol (-17%), triglycerides (-20%) and low-density lipoprotein cholesterol (-17%), cholesterol/high-density lipoprotein (HDL) cholesterol ratio (-21%), apolipoprotein (apo) B/apo A-I ratio (-4%) and factor VII coagulant activity (FVIIc) (-5%) from baseline. These changes were significantly different between the diets (P=0.05 to P<0.0001), except for FVIIc (P=0.1). The RO diet, but not the DF diet, modestly increased serum lipoprotein(a) (+6%) and tended to increase the glucose disappearance rate (K-value, +33%). HDL cholesterol, insulin sensitivity, fibrinogen and tissue plasminogen activator inhibitor-1 levels did not change from baseline or differ between the two diets. CONCLUSIONS: In a diet moderately high in total fat, replacing dairy fat with RO causes a rapid and clinically relevant improvement in serum lipoprotein profile including lowering of triglycerides in hyperlipidaemic individuals.

Essential fatty acid status in teenage girls with eating disorders and weight loss.

AIM: To explore the relationship between essential fatty acids (FA) and weight changes in adolescent girls with eating disorders (ED). METHODS: Blood samples were obtained from 220 girls with ED and 39 healthy controls. The girls with ED were 15.3 ± 1.5 years of age and weighed 49.8 ± 8.7 kg (BMI 18.3 ± 2.8 kg/m(2)) after a weight loss of 6.8 ± 6.4 kg. FA were analysed in plasma phospholipids (PPL) and erythrocyte membranes (ERY). RESULTS: The proportions of saturated and monounsaturated FA were increased during weight loss, while linoleic acid (18:2ω6) was decreased. The proportions of eicosapentanoic acid (EPA) (20:5ω3) and docosahexanoic acid (DHA) (22:6ω3) in PPL and ERY did not differ from controls. The activity of stearoyl-CoA-desaturase was increased as evidenced by an increased product/precursor ratio and correlated with the rate of weight loss. The activities of delta-6-desaturase and delta-5-desaturase did not differ from controls. The rate of weight loss was inversely correlated with delta-6-desaturase and directly correlated with delta-5-desaturase. CONCLUSION: The FA profile indicates low-fat intake, fat mobilization from stores and an increased conversion of essential FA at the delta-5-desaturase step during weight loss in adolescent girls with ED. Normal levels of EPA and DHA were maintained.

Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome--LIPGENE: a European randomized dietary intervention study.

BACKGROUND: Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS. OBJECTIVE: This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS. DESIGN: A free-living, single-blinded dietary intervention study. SUBJECTS AND METHODS: MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined. RESULTS: In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P < 0.01), particularly in men. CONCLUSION: There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.

Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET).

OBJECTIVE: the aim of this study was to investigate the effects of a healthy Nordic diet (ND) on cardiovascular risk factors. DESIGN AND SUBJECTS: in a randomized controlled trial (NORDIET) conducted in Sweden, 88 mildly hypercholesterolaemic subjects were randomly assigned to an ad libitum ND or control diet (subjects' usual Western diet) for 6 weeks. Participants in the ND group were provided with all meals and foods. Primary outcome measurements were low-density lipoprotein (LDL) cholesterol, and secondary outcomes were blood pressure (BP) and insulin sensitivity (fasting insulin and homeostatic model assessment-insulin resistance). The ND was rich in high-fibre plant foods, fruits, berries, vegetables, whole grains, rapeseed oil, nuts, fish and low-fat milk products, but low in salt, added sugars and saturated fats. RESULTS: the ND contained 27%, 52%, 19% and 2% of energy from fat, carbohydrate, protein and alcohol, respectively. In total, 86 of 88 subjects randomly assigned to diet completed the study. Compared with controls, there was a decrease in plasma cholesterol (-16%, P < 0.001), LDL cholesterol (-21%, P < 0.001), high-density lipoprotein (HDL) cholesterol (-5%, P < 0.01), LDL/HDL (-14%, P < 0.01) and apolipoprotein (apo)B/apoA1 (-1%, P < 0.05) in the ND group. The ND reduced insulin (-9%, P = 0.01) and systolic BP by -6.6 ± 13.2 mmHg (-5%, P < 0.05) compared with the control diet. Despite the ad libitum nature of the ND, body weight decreased after 6 weeks in the ND compared with the control group (-4%, P < 0.001). After adjustment for weight change, the significant differences between groups remained for blood lipids, but not for insulin sensitivity or BP. There were no significant differences in diastolic BP or triglyceride or glucose concentrations. CONCLUSIONS: a healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinically relevant levels in hypercholesterolaemic subjects.

Adipose tissue fatty acids and insulin sensitivity in elderly men.

AIMS/HYPOTHESIS: Dietary fatty acids may affect insulin sensitivity. Adipose tissue fatty acid composition partly reflects long-term dietary intake, but data from large studies regarding relationships with insulin sensitivity are lacking. We aimed to determine the association between adipose tissue fatty acids and insulin sensitivity in elderly Swedish men. METHODS: In a cross-sectional analysis of the community-based Uppsala Longitudinal Study of Adult Men (n = 795, mean age 71 years), adipose tissue biopsies were obtained and fatty acid composition was determined by gas-liquid chromatography. Insulin sensitivity was measured directly by a euglycaemic clamp. RESULTS: Palmitic acid (16:0), the major saturated fatty acid (SFA) in the diet and in adipose tissue, was negatively correlated with insulin sensitivity (r = -0.14), as were 16:1 n-7 (r = -0.15), 20:3 n-6 (r = -0.31), 20:4 n-6 (r = -0.38), 22:4 n-6 (r = -0.37) and 22:5 n-3 (r = -0.24; p < 0.001 for all). Some minor SFAs were positively correlated; 12:0 (r = 0.46), 14:0 (r = 0.32), 17:0 (r = 0.21) and 18:0 (r = 0.41; p < 0.001 for all), as were essential polyunsaturated fatty acids (PUFAs) 18:2 n-6 (r = 0.10, p < 0.01) and 18:3 n-3 (r = 0.16, p < 0.001). Docosahexaenoic acid (22:6 n-3) was negatively correlated (r = -0.11, p < 0.01), whereas eicosapentaenoic acid (20:5 n-3) was not (r = -0.02, NS). Most associations diminished or disappeared in lean individuals, indicating an effect of obesity. CONCLUSIONS/INTERPRETATION: Adipose tissue enriched with palmitic acid and depleted of essential PUFAs is associated with insulin resistance. The positive association between minor SFAs and insulin sensitivity merits further investigation.

Which are the greatest recent discoveries and the greatest future challenges in nutrition?

BACKGROUND: Nutrition science aims to create new knowledge, but scientists rarely sit back to reflect on what nutrition research has achieved in recent decades. METHODS: We report the outcome of a 1-day symposium at which the audience was asked to vote on the greatest discoveries in nutrition since 1976 and on the greatest challenges for the coming 30 years. Most of the 128 participants were Dutch scientists working in nutrition or related biomedical and public health fields. Candidate discoveries and challenges were nominated by five invited speakers and by members of the audience. Ballot forms were then prepared on which participants selected one discovery and one challenge. RESULTS: A total of 15 discoveries and 14 challenges were nominated. The audience elected Folic acid prevents birth defects as the greatest discovery in nutrition science since 1976. Controlling obesity and insulin resistance through activity and diet was elected as the greatest challenge for the coming 30 years. This selection was probably biased by the interests and knowledge of the speakers and the audience. For the present review, we therefore added 12 discoveries from the period 1976 to 2006 that we judged worthy of consideration, but that had not been nominated at the meeting. CONCLUSIONS: The meeting did not represent an objective selection process, but it did demonstrate that the past 30 years have yielded major new discoveries in nutrition and health.

Serum and dietary beta-carotene and alpha-tocopherol and incidence of type 2 diabetes mellitus in a community-based study of Swedish men: report from the Uppsala Longitudinal Study of Adult Men (ULSAM) study.

AIMS/HYPOTHESIS: To investigate the association of serum concentrations and dietary intake of beta-carotene and alpha-tocopherol with type 2 diabetes incidence. METHODS: Serum beta-carotene, alpha-tocopherol, lifestyle factors (BMI, physical activity and smoking) and metabolic factors (insulin sensitivity [homeostasis model assessment], acute insulin response and impaired fasting glucose) were analysed in 846 50-year-old non-diabetic Swedish men (participants in the Uppsala Longitudinal Study of Adult Men). Diabetes was identified in 245 participants at reinvestigations after 10, 20 and 27 years. At the 20 year reinvestigation, dietary intake of beta-carotene and alpha-tocopherol, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp) and insulin secretion (early insulin response in OGTT) were determined. RESULTS: The highest tertile of serum beta-carotene at age 50 (>0.335 mumol/l) was associated with 59% lower risk of diabetes during follow-up compared with the lowest tertile (<0.210 mumol/l) after adjustment for lifestyle and metabolic factors (p < 0.01). The highest tertile of lipid-corrected serum alpha-tocopherol at age 50 (>3.67 mumol/mmol) was associated with 46% lower risk of diabetes compared with the lowest tertile (<3.25 mumol/mmol) independently of metabolic factors (p < 0.05). Moreover, lower serum beta-carotene and alpha-tocopherol concentrations were independently associated with impaired insulin sensitivity (p < 0.001), but not with early insulin response, in a subsample of non-diabetic individuals 20 years later. Dietary intake of beta-carotene and alpha-tocopherol independently predicted type 2 diabetes during 7 years of follow-up. CONCLUSIONS/INTERPRETATION: Serum concentrations and dietary intakes of beta-carotene and alpha-tocopherol independently predicted insulin resistance and type 2 diabetes incidence during 27 years of follow-up in a community-based study of men. This result supports the importance of impaired antioxidant status for the development of insulin resistance and type 2 diabetes.

Serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities are related to overweight and cardiovascular risk factors in adolescents.

AIM/HYPOTHESIS: The objective of this study was to describe the relation of serum fatty acids and desaturase activity (DA) to overweight, insulin sensitivity and cardiovascular disease (CVD) risk factors in adolescents. METHODS: The relations of % serum phospholipid (PL) and cholesteryl ester (CE) fatty acids and estimated DA with CVD risk factors were examined in 264 adolescents (average age 15 years). Fatty acids were determined by gas liquid chromotography. Surrogate measures of DA were expressed as ratios of serum fatty acids: Delta9 DA=16:0/16:1; Delta6 DA=20:3,n6/18:2,n6 (PL) or 18:3,n6/18:2,n6 (CE); and Delta5 DA=20:4,n6/20:3,n6. Spearman partial correlations of fatty acids (%) and DA ratios with CVD risk factors were reported, adjusting for age, sex, race, Tanner stage, energy intake and physical activity. RESULTS: Overweight adolescents compared to normal weight had more adverse levels of CVD risk factors, composition of PL and CE fatty acids in serum, and Delta6 DA and Delta5 DA ratios. Linoleic acid was inversely related to body mass index (BMI), waist circumference and triglycerides (P

A high activity index of stearoyl-CoA desaturase is associated with increased risk of fracture in men.

UNLABELLED: The activity index of stearoyl-CoA desaturase (SCD), a key enzyme in lipogenesis, was associated with increased risk of fracture in a longitudinal population-based cohort of men. This indicates that elevated levels of endogenous lipogenesis increase the risk of fracture and suggest a role for saturated fat in the pathogenesis of osteoporosis. INTRODUCTION: Osteoblasts and marrow adipocytes are derived from a common mesenchymal progenitor, and experimental studies have indicated that increased adipogenesis can occur at the expense of osteoblasts, leading to bone loss. Stearoyl-CoA desaturase (SCD) converts saturated to monounsaturated fatty acids and is a key enzyme in lipogenesis. METHODS: Analysis was performed in a population-based, longitudinal cohort study of men (n = 2009). A product-to-precursor index (palmitoleic acid/palmitic acid) was used to estimate SCD activity in fasting serum analyzed in samples obtained at enrollment at age 50 years. Fractures were documented in 422 men during 35 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to SCD activity index. RESULTS: The risk of fracture was highest among men with the highest levels of SCD activity index. Multivariable analysis of the risk of fracture in the highest quintile as compared to the lowest one showed that the rate ratio was 1.71 (95% CI 1.26-2.33) for any fracture, with an estimated population attributable risk of 15%. The risk was further increased within the highest quintile. CONCLUSIONS: Our results indicate that elevated levels of endogenous lipogenesis increase the risk of fracture and suggest a role for saturated fat in the pathogenesis of osteoporosis.

Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance.

AIMS/HYPOTHESIS: Fatty acid desaturases introduce double bonds into growing fatty acid chains. The key desaturases in humans are Delta5-desaturase (D5D), Delta6-desaturase (D6D) and stearoyl-CoA desaturase (SCD). Animal and human data implicate hepatic desaturase activities in insulin resistance, obesity and dyslipidaemia. However, the role of desaturase activity in adipose tissue is uncertain. We therefore evaluated relationships between adipose mRNA expression, estimated desaturase activities (fatty acid ratios) in adipose tissue and insulin resistance. METHODS: Subcutaneous adipose tissue mRNA expression of D5D (also known as FADS1), D6D (also known as FADS2) and SCD was determined in 75 individuals representative of the study population of 294 healthy 63-year-old men. Desaturation indexes (product/substrate fatty acid ratios) were generated from adipose tissue fatty acid composition in all individuals. Insulin resistance was defined as the upper quartile of the updated homeostasis model assessment (HOMA-2) index. RESULTS: The relevant desaturation indexes (16:1/16:0, 18:1/18:0, 20:4/20:3 and 18:3/18:2) reflected expression of SCD, but not of D5D or D6D in adipose tissue. Insulin-resistant individuals had a higher adipose tissue 18:1/18:0, but not 16:1/16:0 ratio than insulin-sensitive individuals. Individuals with a high adipose tissue 18:1/18:0 ratio were 4.4-fold (95% CI 1.8-11.8) more likely to be insulin resistant [threefold (95% CI 1.1-8.6) after adjustment for waist circumference and plasma triacylglycerol]. In a multiple regression model predicting HOMA-2, the independent effect of the 18:1/18:0 ratio was borderline (p=0.086). CONCLUSIONS/INTERPRETATION: Adipose tissue desaturation indexes of SCD reflect the expression of the gene encoding the enzyme in this tissue. Elevated SCD activity within adipose tissue is closely coupled to the development of insulin resistance.

Both cyclooxygenase- and cytokine-mediated inflammation are associated with carotid intima-media thickness.

BACKGROUND: Common carotid artery intima-media thickness (CCA-IMT) is a valid index of atherosclerosis, which is viewed as an inflammatory disease. It is unknown if various modes of inflammation (cyclooxygenase [COX]-mediated, cytokine-mediated), oxidative stress and anti-oxidants are independently related to CCA-IMT. METHODS AND RESULTS: We investigated cross-sectional relations between CCA-IMT measured by B-mode ultrasound and COX-mediated inflammation (as measured by 15-keto-dihydro-prostaglandin F(2alpha) [PGF(2alpha)], cytokine-mediated inflammation (interleukin-6 [IL-6], high sensitivity C-reactive protein [hsCRP] and serum amyloid A protein [SAA]), oxidative stress (8-iso-PGF(2alpha), an F(2)-isoprostane; a non-enzymatic, free radical-induced product of arachidonic acid), and tocopherols (anti-oxidants) in a small subset of a population-based sample of elderly men (n=234) stating no use of anti-inflammatory medications. In a backward-stepwise regression analysis of correlates of CCA-IMT (with PGF(2alpha), hsCRP, IL-6, SAA, F(2)-isoprostanes, tocopherols, diabetes, body mass index (BMI), beta-blocker, statin treatment, smoking, hypertension and cholesterol), PGF(2alpha), CRP, beta-blocker treatment, diabetes and BMI were independently associated with CCA-IMT. There were no associations between F(2)-isoprostanes or tocopherols and CCA-IMT in this study. CONCLUSION: This study suggests both COX- and cytokine-mediated inflammation to be independently associated with increased CCA-IMT, implying that there might be more than one mode of inflammation involved in atherogenesis.

Fatty acid handling protein expression in adipose tissue, fatty acid composition of adipose tissue and serum, and markers of insulin resistance.

OBJECTIVE: Proteins involved in cellular fatty acid (FA) uptake and metabolism may be of relevance in the context of disturbed FA metabolism associated with insulin resistance. Therefore this study investigated relationships between FA handling protein mRNA expression in adipose tissue, FA composition of adipose tissue and serum, and markers of insulin resistance. SUBJECTS: 75 subjects with a range of insulin sensitivities recruited from a cohort of 294 healthy 63-year-old Swedish men. MEASUREMENTS: Anthropometric and biochemical variables (e.g. waist-hip-ratio (WHR) and homeostasis model assessment (HOMA) index of insulin sensitivity), FA composition of the subcutaneous (s.c.) gluteal adipose tissue, serum nonesterified FA (NEFA) and serum phospholipid compartments (by gas-liquid chromatography; n = 294), and mRNA levels of FA handling proteins (adipocyte and keratinocyte lipid binding proteins, fatty acid transport protein (FATP) -1 and -4, CD36/fatty acid translocase, plasma membrane fatty acid binding protein, and acyl-CoA synthase-1 (ACS1)) in s.c. gluteal adipose tissue (by quantitative real-time polymerase chain reaction; n = 75). RESULTS: ACS1 expression was negatively correlated with measures of insulin resistance and central obesity (ACS1 versus HOMA: r = -0.28, P<0.05; ACS1 versus WHR: r = -0.23, P<0.05), with an opposite trend for FATP4. Further analysis of ACS1 expression levels revealed correlations with adipose tissue 16:0 (r = -0.27, P<0.05) and NEFA 16:1 (r = 0.29, P<0.05), FA composition variables which in turn correlated with HOMA index (r = 0.39, P<0.001 and r = -0.23, P<0.05, respectively, n = 75). Moreover, NEFA 16:1 predicted ACS1 expression independently of HOMA, WHR and adipose tissue 16:0 in multiple regression analysis (standardized coefficient = 0.27, P<0.05). CONCLUSION: Significant associations were found between measures of insulin sensitivity, adipose tissue FA handling protein expression, and specific FA composition variables. Although causal relationships could not be identified these findings suggest a role of FA handling proteins in relation to insulin sensitivity, via their involvement in FA trafficking and metabolism. In particular they indicate links between ACS1 activity, the distribution of 16:0 and 16:1, and insulin sensitivity, which may be of physiological relevance.

Plasma antioxidant capacity among middle-aged men: the contribution of uric acid.

OBJECTIVE: Although assays of plasma antioxidant capacity encompass interactions between various antioxidants, uric acid concentration can exert a predominant effect on results. Therefore, individual differences in uric acid concentration may explain a many of the differences in antioxidant capacity. The objective of this study was to measure the antioxidant capacity of plasma samples with and without uric acid in order to provide more information about how the concept of antioxidant capacity could be applied. MATERIAL AND METHODS: Antioxidant capacity was measured using an enhanced chemiluminescence assay, and uric acid was removed from the samples using uricase. RESULTS: Antioxidant capacity was positively correlated with uric acid concentration, body mass index, waist circumference, abdominal sagittal diameter and the concentrations of insulin and triglycerides. These correlations were not evident when uric acid was eliminated from the sample, but antioxidant capacity was correlated with lipid concentration; this may partly reflect tocopherols that are transported by lipid molecules. CONCLUSIONS: The significance of the contribution of uric acid to the antioxidant capacity could differ according to the type of study. Antioxidant capacity measurements in cross-sectional studies may be presented both with and without the contribution of uric acid, because the absence of such data complicates interpretation of results when different populations are compared.

Glucose and insulin responses in healthy women after intake of composite meals containing cod-, milk-, and soy protein.

OBJECTIVE: To evaluate the metabolic effect of three different kinds of dietary proteins as part of composite meals with similar macronutrient composition in healthy subjects. DESIGN: A randomised meal study. SETTING: Metabolic ward. SUBJECTS AND METHODS: In total, 17 healthy women, 30-65 years old, consumed three meals in randomised order. The meals consisted of foodstuffs with similar nutrient composition but different types of protein (cod, cottage cheese, or soy protein isolate). The distribution of energy from protein, fat and carbohydrates was 33, 26, and 41 energy percent, respectively. Total amount of energy was 2300 kJ. Blood samples were drawn for assay of B-glucose, S-insulin, S-free fatty acids, S-triglycerides, and C-peptide in the fasting state and at seven times (20, 40, 60, 90, 120, 180, and 240 min) after starting to eat the test meal. RESULTS: The blood glucose response after the cod protein meal differed from that of the soy protein meal, with a larger area under the curve (AUC) calculated up to 120 min. The serum insulin response after the milk protein meal differed from that of the cod protein meal with a larger AUC calculated up to 240 min. The insulin/C-peptide and the insulin/glucose ratios differed between the meals; the insulin/C-peptide ratio was higher after the milk protein meal compared to the cod, and soy protein meal at 120 min. The insulin/glucose ratio was lower after the cod protein meal compared to the milk, and soy protein meals at 120 min. The results showed that the metabolic responses differed after meals with similar macronutrient composition containing cod-, milk-, or soy protein.

Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men.

AIMS/HYPOTHESIS: Types of dietary fat have been related to components of the metabolic syndrome. Serum fatty acid composition mainly reflects dietary fat intake, but also endogenous fatty acid synthesis catalysed by Delta-desaturases. It is not known whether alterations of fatty acid composition or desaturase activities predict metabolic syndrome. MATERIALS AND METHODS: We prospectively evaluated fatty acid composition in serum cholesteryl esters and estimated desaturase activities in 1,558 50-year-old men taking part in a population-based cohort study. The follow-up time was 20 years. Stearoyl-CoA desaturase (SCD-1), Delta6 (D6D) and Delta5 (D5D) desaturases were estimated as precursor to fatty acid ratios. RESULTS: High activity of estimated SCD-1 (odds ratio=1.29, p<0.05) and D6D (odds ratio=1.35, p<0.05), as well as low estimated D5D activity (odds ratio=0.71, p<0.001) predicted the development of metabolic syndrome (as defined by the National Cholesterol Education Program). The predictive value of D5D activity was independent of lifestyle factors (smoking, BMI and physical activity), whereas the risk associated with higher SCD-1 and D6D activities was mainly explained by obesity. Among those developing metabolic syndrome (119 out of 706) during follow-up, the proportions of fatty acids 14:0, 16:0, 16:1 (n-7), 18:1 (n-9), 18:3 (n-6) and 20:3 (n-6) were increased at baseline, while 18:2 (n-6) was decreased (p<0.05 for all). CONCLUSIONS/INTERPRETATION: Serum fatty acid composition predicts the long-term development of the metabolic syndrome, and D5D activity may be particularly important in this process. Our results suggest a role of dietary fat quality in the development of metabolic syndrome, but the possibility that altered fatty acid composition, partly secondary to genetic or hormonal factors, should also be considered.

Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F2-isoprostane formation in elderly men.

The underlying mechanisms by which smoking induces cardiovascular diseases are largely unknown. The effect of smoking status on the cyclooxygenase (COX)-mediated inflammatory indicator prostaglandin F(2alpha) (PGF(2alpha)) has never been studied. Associations of cytokines and antioxidants and smoking status, have shown conflicting results. Urinary 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha)), serum interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), serum amyloid protein A (SAA), urinary 8-iso-PGF(2alpha) (an F(2)-isoprostane, indicator of oxidative stress), and serum alpha-tocopherol were quantified in a population-based sample (n = 642) of 77-year old men without diabetes. Fifty-five men were current smokers and 391 former smokers. Inflammatory indicators were increased in current smokers (15-keto-dihydro-PGF(2alpha), P < 0.001; IL-6, P = 0.01) than non-smokers. 8-iso-PGF(2alpha) was increased (P < 0.01) and alpha-tocopherol reduced (P < 0.001) in current smokers. Further, former smokers had increased formation of 15-keto-dihydro-PGF(2alpha), IL-6 and 8-iso-PGF(2alpha) compared non-smokers. This is the first study to show that smokers have increased PGF(2alpha) formation, thus enhanced COX-mediated inflammation, in addition to elevated levels of cytokines and isoprostanes. Subclinical COX- and cytokine-mediated inflammation and oxidative stress are ongoing processes not only in active smokers but also in former smokers which may contribute to the accelerated atherosclerosis associated with smoking.