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Purpose: The aim of this study was to investigate the association between adipose tissue content of the plant-derived n-3 fatty acid, alpha-linolenic acid, and the rate of incident peripheral artery disease (PAD)., Methods: We conducted a case-cohort study nested within the Danish Diet, Cancer and Health cohort (n = 57,053), which was established between 1993 and 1997. Potential PAD cases were identified using linkage with The Danish National Patient Register and all potential cases were validated. Adipose tissue samples from the buttock were collected at baseline and fatty acid composition was determined in cases and in a random sample (n = 3500) from the cohort by gas chromatography. Statistical analyses were performed using weighted Cox regression allowing for different baseline hazards among sexes., Results: During a median of 13.5 years of follow-up, we identified 863 PAD cases with complete information. The median adipose tissue content of ALA in the sub-cohort (n = 3197) was 0.84% (interquartile range 0.73-0.94%) of total fatty acids. In multivariate analyses including adjustment for established risk factors, we observed a U-shaped association between ALA in adipose tissue and rate of PAD, but the association was not statistically significant (P = 0.131). Similar pattern of associations were observed between ALA content in adipose tissue and the rate of PAD among men and women., Conclusions: We found indications of a U-shaped association between adipose tissue content of ALA and the rate of PAD, but the association was not statistically significant.

Diet, with its content of various types of fatty acids (FAs), is of great importance for cellular function. Adipose tissue (AT) serves as a storage for dietary FAs, but after appropriate activation it may also offer important biological properties, e.g., by releasing adipokines and cytokines to the surrounding milieu. Such effects may depend on the diet and type of FA involved. Similarly, the composition of FAs in the heart is also likely to be important for cardiac function. We investigated samples of epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), subcutaneous adipose tissue (SCAT), and tissue from the right atrial appendage to compare the FA compositions in patients undergoing elective cardiac surgery. Minor differences among AT compartments were found, while the comparison of atrial tissue and EAT showed major differences in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n -3 and n -6 polyunsaturated fatty acids (PUFAs). These findings may be of importance for understanding biological availability, dietary effects, and the effects of FAs on the heart.

Background: The content of marine n-3 polyunsaturated fatty acids (PUFAs) in adipose tissue is considered a long-term biomarker for the body's endogenous exposure to seafood., Objectives: This study sought to examine associations between the content of marine n-3 PUFAs in adipose tissue and the risk of incident peripheral arterial disease (PAD)., Methods: In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, adipose tissue biopsies were taken from the buttocks of all participants at baseline. After a median follow-up of 13.5 years, 870 validated cases of PAD were identified and included together with a randomly drawn subcohort of 3,204 participants using weighted Cox regression. Adipose tissue samples were analyzed by gas chromatography., Results: In multivariable analyses using the lowest quintile as the reference and adjusting for established risk factors for PAD, we found a statistically significant lower rate of PAD in the highest quintile of eicosapentaenoic acid (EPA) (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.41 to 0.74) and a nonsignificant lower rate for docosahexaenoic acid (HR: 0.79; 95% CI: 0.59 to 1.06). We observed a lower rate of PAD, when comparing the highest quintile of the combined EPA and docosahexaenoic acid with the reference (HR: 0.71; 95% CI: 0.53 to 0.96). In contrast, docosapentaenoic acid had an HR of 1.31 (95% CI: 0.97 to 1.77) in the highest quintile., Conclusions: A high content of marine n-3 PUFAs in adipose tissue, in particular EPA, was associated with a lower risk of incident PAD., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The risk of coronary heart disease associated with intake of individual trans fatty acids (TFAs) is not clear. Adipose tissue content of TFAs is a biomarker of TFA intake and metabolism., Objective: We investigated the rate of myocardial infarction (MI) associated with the adipose tissue content of total 18:1t, isomers of 18:1t (18:1 Δ6-10t and 18:1 Δ11t) and 18:2 Δ9c, 11t., Methods: A case-cohort study, nested within the Danish Diet, Cancer and Health cohort (n = 57,053), was conducted, which included a random sample (n = 3156) of the total cohort and all incident MI cases (n = 2148) during follow-up (14 years). Information on MI cases was obtained by linkage with nationwide registers and validated. Adipose tissue was taken from the participants buttocks and the fatty acid composition was determined by gas chromatography., Results: Women with higher adipose tissue content of total 18:1t had a 57% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.57; 95% confidence interval, 1.12-2.20; P-trend = 0.011) and women with higher content of 18:1 Δ6-10t had a 76% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.76; 95% confidence interval, 1.23-2.51; P-trend = 0.002). No association between 18:1 Δ11t content and MI rate was observed. In men, no associations between adipose tissue content of total 18:1t and 18:1 Δ6-10t and MI rate were observed. However, men with higher content of 18:1 Δ11t had a 48% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.48; 95% confidence interval, 1.17-1.86; P-trend = 0.003). Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men., Conclusions: Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men, whereas higher contents of isomers of 18:1t were associated with higher MI rates but the associations for individual 18:1t isomers differed, however, in women and men., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The aim of this study was to investigate the association between adipose tissue content of total saturated fatty acids including myristic (C14:0), palmitic (C16:0) and stearic (C18:0) acid, as a measure of exposure to saturated fatty acids and the risk of incident atrial fibrillation., Materials and Methods: A total of 57 053 Danish men and women aged 50-64 years participating in the Diet, Cancer and Health cohort had an adipose tissue biopsy taken at baseline, and this was analysed for saturated fatty acids content by gas chromatography. Follow-up was registry based and in this case-cohort study we used all cases and a randomly drawn subcohort of 3500 participants representative for the entire cohort., Results: Data were analysed using weighted Cox proportional hazards regression. During a median follow-up of 14.6 years, a total of 4722 cases of incident atrial fibrillation were diagnosed. For both men and women, no association between adipose tissue content of total saturated fatty acids and the risk of atrial fibrillation could be demonstrated., Conclusion: We did not find an association between adipose tissue content of total saturated fatty acids and the risk of incident atrial fibrillation., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: The 5-lipoxygenase pathway has been linked to atherothrombotic disease, and a functional tandem repeat polymorphism in the arachidonate lipoxygenase-5 ( ALOX-5 ) gene has been associated with the risk of myocardial infarction (MI). Interestingly, 2 studies have reported an interaction between dietary intakes of the ALOX-5 substrates, arachidonic acid (AA) and eicosapentaenoic acid (EPA), and genotype. Objective: We investigated whether the interactions between the ALOX-5 tandem repeat polymorphism (rs59439148) and adipose tissue AA and EPA were associated with incident MI. Methods: In the Danish Diet, Cancer and Health study, we conducted a case-cohort study including 3089 participants with incident MI identified from national registries and a randomly selected subcohort of 3000 participants. Participants were men and women with a median age of 56 y at baseline and no previous history of cancer. Adipose tissue and blood samples were collected at baseline along with comprehensive questionnaires on lifestyle and demographic data. The ALOX-5 tandem repeat polymorphism was genotyped by multititer plate sequencing. Associations were analyzed by using Cox proportional hazards models. Results: We observed a higher risk of MI for homozygous carriers of the variant alleles in the fifth quintile of AA content than for the reference group with the lowest quintile of AA and carrying the wild-type allele (HR: 3.02; 95% CI: 1.41, 6.44). In contrast, homozygotes for the variant alleles tended to have a higher risk of MI when comparing the lowest quintile of EPA content with the reference group with the highest quintile of EPA and carrying the wild-type allele (HR: 2.15; 95% CI: 0.91, 5.09; P = 0.08). Although our results suggested interactions between the polymorphism and adipose tissue AA and EPA, a quantitative evaluation of interaction by calculating the relative excess risk due to interactions was not significant. Conclusions: Adipose tissue EPA and AA and the ALOX-5 tandem repeat polymorphism did not significantly interact to affect the risk of MI. However, the results should be replicated in larger, heterogeneous populations., Competing Interests: Author disclosures: AG, SL-C, AT, EBS, KO, and MSN, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: Adding long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) to a rodent diet reduces fat mass and prevents the development of obesity, but evidence of a similar effect in humans is rather limited. Objectives: We investigated the associations between dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference in humans. Effect modification by the carbohydrate:protein ratio and glycemic index was also investigated. Design: A total of 29,152 participants included in the Diet, Cancer, and Health cohort were followed. Dietary intake was assessed with the use of a validated 192-item semiquantitative food-frequency questionnaire. Adipose tissue content of fatty acids was determined by gas chromatography in a random sample of the cohort ( n = 1660). Anthropometric measurements were taken at baseline and 5 y later. Associations were investigated with the use of a linear regression model. Results: For high (1.22 g/d) compared with low (0.28 g/d) total n-3 PUFA intake, the difference in 5-y weight change was 147.6 g (95% CI: -42.3, 337.5 g); P -trend = 0.088. No associations between the individual n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were observed. Intake of n-3 PUFAs was not associated with a 5-y change in waist circumference. For high (0.16%) compared with low (0.06%) adipose tissue content of EPA, the difference in 5-y weight change was -649.6 g (95% CI: -1254.2, -44.9 g); P -trend = 0.027. No associations between total n-3 PUFA, docosapentaenoic acid, and docosahexaenoic acid and 5-y weight change were observed. Adipose tissue content of n-3 PUFAs was not associated with 5-y change in waist circumference. No effect modification by carbohydrate:protein ratio or glycemic index was found. Conclusion: Dietary intake and adipose tissue content of long-chain n-3 PUFAs were neither consistently nor appreciably associated with change in body weight or waist circumference., (© 2017 American Society for Nutrition.)

Background: Patients with chronic kidney disease have a markedly increased cardiovascular mortality compared with the general population. Long chain n-3 polyunsaturated fatty acids have been suggested to possess cardioprotective properties. This cross-sectional and comparative study evaluated correlations between hemodynamic measurements, resistance artery function and fish consumption to the content of long chain n-3 polyunsaturated fatty acids in adipose tissue, a long-term marker of seafood intake., Methods: Seventeen patients with chronic kidney disease stage 5 + 5d and 27 healthy kidney donors were evaluated with hemodynamic measurements before surgery; from these subjects, 11 patients and 11 healthy subjects had vasodilator properties of subcutaneous resistance arteries examined. The measurements were correlated to adipose tissue n-3 polyunsaturated fatty acids. Information on fish intake was obtained from a dietary questionnaire and compared with adipose tissue n-3 polyunsaturated fatty acids., Results: Fish intake and the content of n-3 polyunsaturated fatty acids in adipose tissue did not differ between patients and controls. n-3 polyunsaturated fatty acid levels in adipose tissue were positively correlated to systemic vascular resistance index; (r = 0.44; p = 0.07 and r = 0.62; p < 0.05, chronic kidney disease and healthy subjects respectively) and negatively correlated to cardiac output index (r = -0.69; p < 0.01 and r = -0.50; p < 0.05, chronic kidney disease and healthy subjects respectively). No correlation was observed between n-3 polyunsaturated fatty acid levels in adipose tissue and vasodilator properties in resistance arteries. n-3 PUFA content in adipose tissue increased with increasing self-reported fish intake., Conclusions: The correlations found, suggest a role for n-3 polyunsaturated fatty acids in hemodynamic properties. However, this is apparently not due to changes in intrinsic properties of the resistance arteries as no correlation was found to n-3 polyunsaturated fatty acids.

Background: Intake of the plant-derived ω-3 (n-3) fatty acid α-linolenic acid (ALA, 18:3; n-3) may reduce coronary heart disease (CHD) risk, but the results of previous studies have been inconsistent., Objective: We aimed to investigate the association between dietary intake of ALA, adipose tissue content of ALA, and risk of incident myocardial infarction (MI)., Design: A total of 57,053 participants, aged 50-64 y, were enrolled in the prospective Danish cohort study Diet, Cancer and Health between 1993 and 1997. Dietary intake of ALA was assessed with the use of a validated semiquantitative food-frequency questionnaire in the full cohort, whereas the adipose tissue content of ALA was determined with the use of gas chromatography in all incident MI cases and in a random sex-stratified sample of the total cohort (n = 3500)., Results: During a median of 17 y of follow-up, we identified 2177 male and 912 female cases of MI. After appropriate exclusions, we included 2124 men and 854 women for analyses of dietary intake of ALA, whereas 1994 men and 770 women were included in the analysis of the adipose tissue content of ALA. In multivariate analyses that were conducted with the use of restricted cubic splines and adjusted for established CHD risk factors, weak positive associations in men and weak U-shaped associations in women were shown between both dietary intake and the adipose tissue content of ALA and risk of MI, but these associations were not statistically significant. Additional adjustments for dietary factors did not influence the observed associations numerically., Conclusion: This study suggests that ALA has no appreciable association with risk of incident MI in either men or women., (© 2016 American Society for Nutrition.)

Background: The content of arachidonic acid in adipose tissue is positively associated with the risk of myocardial infarction, whereas the content of eicosapentaenoic acid in adipose tissue has been reported to be negatively associated with the risk of myocardial infarction. Both arachidonic acid and eicosapentaenoic acid are substrates for the synthesis of pro-inflammatory leukotrienes and leukotrienes derived from eicosapentaenoic acid are generally much less potent. In this study we hypothesized that a high content of arachidonic acid in adipose tissue would reflect a high formation of arachidonic acid derived leukotrienes and a high expression of 5-lipoxygenase in atherosclerotic plaques. Likewise, we hypothesized that a high content of eicosapentaenoic acid in adipose tissue would reflect a low formation of arachidonic acid derived leukotrienes and a low expression of 5-lipoxygenase in plaques., Methods: In a cross sectional study we included 45 consecutive subjects undergoing femoral thrombendarterectomy. The expression of 5-lipoxygenase in plaques was assessed by a semi-automated image analysis computer programme after immunohistochemical staining with mono-clonal 5-lipoxygenase antibodies. Leukotriene B4 and cysteinyl leukotriene formation from stimulated femoral artery plaques was quantified using ELISA methods. The fatty acid content of adipose tissue biopsies from the thigh was analyzed using gas chromatography. Associations between variables were assessed by Pearson correlations and were further explored in a multivariable linear regression model adjusting for potential confounders., Results: A high content of arachidonic acid in adipose tissue was associated with a higher expression of 5-lipoxygenase in plaques (r = 0.32, p = 0.03), but no significant associations with leukotriene B4 (r = 0.22, p = 0.14) and cysteinyl leukotriene (r = -0.11, p = 0.46) formation was seen. No significant associations were found between the content of eicosapentaenoic acid in adipose tissue and 5-lipoxygenase expression or leukotriene formation in plaque., Conclusions: Adipose tissue arachidonic acid contents correlated positively with the expression of 5-lipoxygenase in plaques. This association might represent a causal link between adipose tissue arachidonic acid and the risk of myocardial infarction but confirmatory studies are needed.

The primary aim of the trial was to investigate the influence of menopause on the incorporation of marine n-3 PUFA into platelets and adipose tissue. A secondary aim was to evaluate whether marine n-3 PUFA may change levels of circulating oestrogens in women. Ninety-two pre- and postmenopausal women were randomly assigned to consume 2.2 g of marine n-3 PUFA or control oil daily for 12 weeks. Adipose tissue biopsies and blood samples were collected at baseline and after intervention. Eighty-nine women completed the study. Baseline contents of total marine n-3 PUFA and each of the major long-chained n-3 PUFA, EPA, docosapentaenoic acid and DHA were all significantly lower (P < 0.05) in the premenopausal group both in platelets and adipose tissue, except for EPA in platelets (P = 0.05). After supplementation with fish oil, the content of all marine n-3 PUFA increased significantly in platelets and adipose tissue in both pre- and postmenopausal women. The increase in platelets and adipose tissue was, however, the same in both groups. There was no effect of fish oil on oestrogen levels in postmenopausal women. We found a significant difference in premenopausal women, in whom oestradiol (P < 0.04) and oestrone (P < 0.02) serum concentrations increased after the fish oil supplement. This trial did not reveal any difference in the ability of pre- and postmenopausal women to incorporate marine n-3 PUFA into platelets or adipose tissue. However, supplementation with fish oil increased oestrogen levels in premenopausal women.

Objective: The aim of this study was to investigate the association between the content of marine n-3 polyunsaturated fatty acids (PUFA) in adipose tissue, a biomarker for the long-term intake of seafood, and the subsequent development of breast cancer (BC)., Design: We designed a case-cohort study based on a cohort of healthy Danish women, who in the 1990 s donated adipose tissue biopsies to a biobank in order to investigate the role of diet for the development of cancer and chronic disease. During follow-up, incident cases of BC were identified through national registries, and the content of n-3 PUFA in adipose tissue was compared between cases and the cohort sample., Results: During follow-up, 463 new cases of BC were identified. After adjusting for potential confounders, no significant association between the content of marine n-3 PUFA and BC was found. When comparing the highest with the lowest quintile, the hazard ratio (HR) was 0.96 (95% CI 0.64-1.43) for total marine n-3 PUFA, 0.84 (95% CI 0.58-1.23) for eicosapentaenoic acid (EPA), and 1.08 (95% CI 0.73-1.58) for docosahexaenoic acid (DHA)., Conclusion: This study does not indicate any association between the content of total or individual marine n-3 PUFA in adipose tissue and development of BC.

Background: Intake of the plant-derived ω3 (n-3) fatty acid α-linolenic acid (ALA, 18:3; n-3) may reduce coronary heart disease (CHD) risk, but the results of previous studies have been inconsistent. Objective: We aimed to investigate the association between dietary intake of ALA, adipose tissue content of ALA, and risk of incident myocardial infarction (MI). Design: A total of 57,053 participants, aged 50-64 y, were enrolled in the prospective Danish cohort study Diet, Cancer and Health between 1993 and 1997. Dietary intake of ALA was assessed with the use of a validated semiquantitative food-frequency questionnaire in the full cohort, whereas the adipose tissue content of ALA was determined with the use of gas chromatography in all incident MI cases and in a random sex-stratified sample of the total cohort (n = 3500). Results: During a median of 17 y of follow-up, we identified 2177 male and 912 female cases of MI. After appropriate exclusions, we included 2124 men and 854 women for analyses of dietary intake of ALA, whereas 1994 men and 770 women were included in the analysis of the adipose tissue content of ALA. In multivariate analyses that were conducted with the use of restricted cubic splines and adjusted for established CHD risk factors, weak positive associations in men and weak U-shaped associations in women were shown between both dietary intake and the adipose tissue content of ALA and risk of MI, but these associations were not statistically significant. Additional adjustments for dietary factors did not influence the observed associations numerically. Conclusion: This study suggests that ALA has no appreciable association with risk of incident MI in either men or women. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that the intake of trans-fatty acids (TFA) plays a role in the development of obesity. The proportions of adipose tissue fatty acids not synthesised endogenously in humans, such as TFA, usually correlate well with the dietary intake. Hence, the use of these biomarkers may provide a more accurate measure of habitual TFA intake than that obtained with dietary questionnaires. The objective of the present study was to investigate the associations between the proportions of specific TFA in adipose tissue and subsequent changes in weight and waist circumference (WC). The relative content of fatty acids in adipose tissue biopsies from a random sample of 996 men and women aged 50–64 years drawn from a Danish cohort study was determined by GC. Baseline data on weight, WC and potential confounders were available together with information on weight and WC 5 years after enrolment. The exposure measures were total trans-octadecenoic acids (18 : 1t), 18 : 1 Δ6-10t, vaccenic acid (18 : 1 Δ11t) and rumenic acid (18 : 2 Δ9c, 11t). Data were analysed using multiple regression with cubic spline modelling. The median proportion of total adipose tissue 18 : 1t was 1·52 % (90 % central range 0·98, 2·19) in men and 1·47 % (1·01, 2·19) in women. No significant associations were observed between the proportions of total 18 : 1t, 18 : 1 Δ6-10t, vaccenic acid or rumenic acid and changes in weight or WC. The present study suggests that the proportions of specific TFA in adipose tissue are not associated with subsequent changes in weight or WC within the exposure range observed in this population. [ABSTRACT FROM PUBLISHER]

Objective To investigate whether a supplement of 2.2 g of marine n-3 polyunsaturated fatty acids (PUFA) influences plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels in pre- and postmenopausal women. Methods Ninety-two healthy women were randomly assigned to consume 2.2 g marine n-3 PUFA or a control oil (thistle oil) daily for 12 weeks. Adipose tissue, a long-term marker of dietary intake of seafood was collected at baseline and blood samples were drawn at baseline and after 12 weeks of supplement intake. Results Plasma PCSK9 levels were significantly reduced by 11.4% for premenopausal women and 9.8% for postmenopausal women after the supplement of 2.2 g of marine n-3 PUFA compared with control oil. The mean change of plasma PCSK9 levels between participants receiving marine n-3 PUFA and control oil was 16.1% for premenopausal women and 13.1% for postmenopausal women. There was, however, no correlation between baseline levels of plasma PCSK9 and the fatty acid content of marine n-3 PUFA in adipose tissue. Conclusion This study showed that 2.2 g marine n-3 PUFA reduce plasma PCSK9 levels in both pre- and postmenopausal women. [ABSTRACT FROM AUTHOR]