M. Rosell

Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance

Fatty acid composition of serum lipids and adipose tissue triacylglycerols (AT-TAG) partly reflect dietary fatty acid intake. The fatty acid composition is, besides the diet, also influenced by desaturating enzymes that can be estimated using product-to-precursor fatty acid ratios. The interrelationships between desaturase indices derived from different serum lipid fractions and adipose tissue are unclear, as well as their associations with obesity and insulin resistance. We aimed to investigate cross-sectional correlations between desaturase indices as measured in serum lipid fractions (phospholipids; PL and free fatty acids; FFA) and in adipose tissue (AT-TAG). In a population-based sample of 301 healthy 60-year-old men various desaturase indices were assessed: stearoyl-CoA-desaturase (16:1n-7/16:0; SCD-16 and 18:1n-9/18:0; SCD-18, respectively), delta-6-desaturase (20:3n-6/18:2n-6; D6D) and delta-5-desaturase (20:4n-6/20:3n-6; D5D). Correlations with BMI and insulin resistance (HOMA-IR) were also examined. SCD-16 and D5D were significantly correlated between fractions and tissues (all r > 0.30), whereas SCD-18 and D6D were not. Desaturase indices in serum FFA and AT-TAG were significantly correlated; SCD-16 (r = 0.63), SCD-18 (r = 0.37), and D5D (r = 0.43). In phospholipids, SCD-16 was positively correlated to BMI (r = 0.15), while D5D negatively to both BMI (r = -0.30) and HOMA-IR (r = -0.31), all p < 0.01. D6D in both phospholipids and AT-TAG was positively correlated to HOMA-IR and BMI (all p < 0.01). In conclusion, SCD-1 and D5D activity indices showed overall strong correlations between lipid pools. SCD-1 activity index in adipose tissue is best reflected by 16:1/16:0-ratio in serum FFA, but associations with obesity and insulin resistance differ between these pools. D5D in PL was inversely related to obesity and insulin resistance, whereas D6D index showed positive associations.

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

Aims/hypothesisFatty acid desaturases introduce double bonds into growing fatty acid chains. The key desaturases in humans are Δ5-desaturase (D5D), Δ6-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.MethodsSubcutaneous 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.ResultsThe 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/interpretationAdipose 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.

Low prevalence of the metabolic syndrome in wine drinkers: is it the alcohol beverage or the lifestyle?

Objective: To study how the intake of alcohol and the choice of wine, beer, and spirits is related to lifestyle factors and the metabolic syndrome in 60-y-old men and women.Design: Cross-sectional population based study.Setting: Stockholm County, Sweden.Subjects: Sixty-year-old men and women (n=4232).Results: Moderate intake of wine (10–30 g/day) was associated with a lifestyle characterized by being married, having a university education, being employed, being Swedish-born, having a good quality of life according to economy, leisure time and health, compared with a group with low alcohol intake. The opposite characteristics were seen among the non-drinkers. Drinkers of spirits were more often smokers and also reported higher intake of sausage and fried potatoes compared with a group with low alcohol intake. In women, the metabolic syndrome was significantly more common in non-drinkers (20%), P<0.05, and less common among wine drinkers (8%), P<0.01, compared with a group with low alcohol intake. After adjustments, a significant lower odds ratio for the metabolic syndrome were seen in wine drinkers in women (OR=0.60, P<0.05).Conclusion: Compared with low alcohol drinkers, moderate wine drinkers exhibited a more favorable pattern according to both lifestyle factors and metabolic parameters. The close link between alcohol drinking behaviour and lifestyle habits illustrate the complex relationship between alcohol and health.Sponsorship: Swedish Heart-Lung Foundation, the Stockholm City County Council, the Swedish Society for Medicine, and the Swedish Medical Research Council.

Measures of Oxidized Low-Density Lipoprotein and Oxidative Stress Are Not Related and Not Elevated in Otherwise Healthy Men With the Metabolic Syndrome

Objective—The metabolic syndrome predisposes to the development of cardiovascular diseases. Oxidative stress and elevated circulating oxidized low-density lipoprotein (LDL) concentrations are related to cardiovascular disease and proposed to be features of the metabolic syndrome. F2-isoprostanes are lipid peroxidation products and considered the most reliable biomarkers of oxidative stress. Methods and Results—Plasma oxidized LDL (oxLDL) and urinary 8-iso-prostaglandin F2&agr; (8-iso-PGF2&agr;; the major F2-isoprostane) were analyzed in a cross-sectional study of 289 healthy men (62 to 64 years of age). Individuals completed a 7-day dietary record, and fasting plasma insulin, lipid, and lipoprotein concentrations, LDL particle size, and inflammatory markers were determined. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII) criteria were used to define the metabolic syndrome and individuals were grouped according to the number of risk factors for the metabolic syndrome (0, [n=88; 30%]; ≥1, [n=179; 62%], metabolic syndrome [n=22; 8%]). Group comparisons revealed no differences for oxLDL, 8-iso-PGF2&agr;, or reported intake of macronutrients, whereas C-reactive protein and interleukin-6 were increased in the metabolic syndrome. LDL cholesterol strongly determined oxLDL in univariate and multivariate analysis, but no relationship to 8-iso-PGF2&agr; was found. In turn, 8-iso-PGF2&agr; was related to reported intake of fat, fatty acids, and dietary antioxidants. Conclusions—There were no increases in plasma oxLDL or measures of oxidative stress (urinary 8-iso-PGF2&agr;) in these otherwise healthy 63-year-old men with the metabolic syndrome. Furthermore, no relationship between oxLDL and 8-iso-PGF2&agr; was found, but our results suggest a role for dietary factors in oxidative stress.

Eating meals irregularly: a novel environmental risk factor for the metabolic syndrome.

Background: Skipping meals is a common practice in our current society; however, it is not clear whether eating meals regularly is associated with the metabolic syndrome.

Dietary fish and fish oil and the risk of rheumatoid arthritis.

Background: Intake of fish oil and oily fish has been reported to improve clinical symptoms in people who have rheumatoid arthritis. Whether the intake of oily fish and fish oil might also protect against the development of rheumatoid arthritis is not known. Objective: We investigated the association between intake of oily fish and fish oil supplements and the risk of rheumatoid arthritis in a population-based case-control study. Methods: The study comprised 1889 incident cases of rheumatoid arthritis and 2145 randomly selected controls recruited from a geographically defined area of Sweden during 1996–2005. Data on the consumption of oily fish and fish oil supplements 5 years preceding enrollment had been obtained through a questionnaire. We calculated odds ratios (ORs) for the development of rheumatoid arthritis, using logistic regression to adjust for age, residential area, body mass index, smoking, and alcohol consumption. Results: Compared with subjects who never or seldom consumed oily fish, the OR for developing rheumatoid arthritis was 0.8 (95% confidence interval = 0.6–1.0) for subjects who consumed oily fish 1–7 times a week. The results did not change notably when stratifying the cases for rheumatoid factor or for antibodies to citrullinated peptide antigens. Similar results were seen for subjects consuming oily fish 1–3 times a month. Cases and controls did not differ in their consumption of fish oil supplements. Conclusion: Intake of oily fish was associated with a modestly decreased risk of developing rheumatoid arthritis.

Associations between the intake of dairy fat and calcium and abdominal obesity

OBJECTIVE: This study evaluates the association between abdominal obesity and the intake of dairy fat and calcium using information from dietary data and the relative content of the fatty acids 14:0, 15:0, and 17 : 0 in serum phospholipids (PL) and adipose tissue (AT), which are suggested biological markers for dairy fat intake. This study also explores how the associations were affected when under-reporters (URs) were separated from the analyses.DESIGN: Cross-sectional study.SUBJECTS: In all, 301 healthy 63-y-old men with different degrees of fasting-insulin concentrations.METHODS: Sagittal abdominal obesity (SAD), dietary intake assessed by a 7-day food registration, and the fatty acid composition in serum PL and AT were measured. URs (n=88) and non-under-reporters (non-URs, n=213) were identified by Goldbergs equation, which compares energy intake with energy expenditure, both expressed as multiples of the basal metabolic rate.RESULTS: The intake of dairy fat, expressed as g/100 g fat, was inversely correlated with SAD; however, this association was only observed in the URs (r=−0.36, P=0.001) and not in the non-URs (r=−0.04, P=0.59). The intake of calcium was inversely correlated with SAD in both groups, although the association was weaker in the non-URs. The intake of dairy fat was related to the relative content of the fatty acids 14:0, 15:0, and 17 : 0 in serum PL and AT (r ranging between 0.32 and 0.55). When these fatty acids were correlated to SAD, inverse associations were seen except for 14:0 in PL (r ranging between −0.17 and −0.29.CONCLUSION: If there is a true inverse association between the intake of dairy fat and SAD, it remains to explain why this association was not seen in the non-URs. The data gave some indications of an inverse association between SAD and the intake of calcium. The diverse findings observed when the URs and non-URs were separated highlight the question of how to use and interpret dietary data in URs when diet–disease relationships are investigated.

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.

The relation between alcohol intake and physical activity and the fatty acids 14 : 0, 15 : 0 and 17 : 0 in serum phospholipids and adipose tissue used as markers for dairy fat intake.

The relative contents of the fatty acids 14 : 0, 15 : 0 and 17 : 0 in serum and adipose tissue may be used as biological markers of dairy fat intake. However, the determinants of these fatty acids are not fully understood. This study investigates the relationship between these fatty acids and the intake of macronutrients and physical activity in a cross-sectional study of 301 healthy men aged 61-64 years. Dietary intake was assessed using a pre-coded 7 d food record, and physical activity during the previous year was recorded in an interview. Under-reporters of energy intake were identified by the Goldberg cut-off. Fatty acid composition was determined in serum phospholipids (PL) and subcutaneous adipose tissue (AT) from the upper buttock. The relative content of each of 14 : 0, 15 : 0 and 17 : 0 in PL and AT was positively associated with the intake of dairy fat. In addition, all three fatty acids were inversely correlated with alcohol intake, R ranging from -0.28 to -0.53 (P<0.001). The results were not markedly affected when under-reporters (n 88) were excluded from the analyses. In both PL and AT, the relative content of the fatty acids was approximately 5% higher in a group of high physical activity compared with a group of low physical activity, although significant trends were only seen for 14 : 0 in PL and 17 : 0 in AT. The findings suggest that adjustments should be made for alcohol intake when the fatty acids 14 : 0, 15 : 0 and 17 : 0 are applied as markers for dairy fat intake.

Contribution of a manually coded part in an optically readable, precoded sevenday food record for the intake of energy, nutrients and foods

Objective: This study investigated the contribution of a manually coded part (MP) in a precoded 7 day food record for the intake of energy, nutrients and foods. Design: The dietary intake was assessed in a cross-sectional study using an optically readable precoded 7 day food record. Biological markers for the intakes of protein, sodium and potassium were measured in 24 h urine samples. Underreporters were identified according to the Goldberg cut-off for energy intake:basal metabolic rate. The study setting was an outpatient clinic at Karolinska Hospital, Stockholm, Sweden. The subjects were 301 healthy men aged 63 years. Results: The MP represented 20% of the energy intake. Intakes recorded as free text were foods commonly eaten between meals, especially in the evening and were, with the exception of fruits, characterized as less healthy. The agreement between using the food record with and without the MP, respectively, was low for energy, carbohydrates, a-tocophe rol and vitamin C, and high for retinol, vitamin D and vitamin B12. Underreporters recorded their food intake as free text to a lesser degree than did non-underreporters. When the MP was included in the food record, the percentage of energy from fat and carbohydrates increased and the percentage of energy from protein decreased. The biological markers for protein, sodium and potassium confirmed an improved validity of the dietary data when the MP was included. Conclusions: Inclusion of the food consumption recorded in free text influenced the dietary quality and indicated improved validity of the optically readable precoded food record. To increase the possibility of catching underreporting in dietary surveys, these findings emphasize the importance of the recording/ reporting of between-meal eating. Keywords: biological markers; dietary assessment; in-between meals; precoded food record; underreporting