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1.  Children and young adults with familial hypercholesterolaemia (FH) have healthier food choices particularly with respect to dietary fat sources compared with non-FH children 
Familial hypercholesterolaemia (FH) leads to elevated plasma levels of LDL-cholesterol and increased risk of premature atherosclerosis. Dietary treatment is recommended to all patients with FH in combination with lipid-lowering drug therapy. Little is known about how children with FH and their parents respond to dietary advice. The aim of the present study was to characterise the dietary habits in children with FH. A total of 112 children and young adults with FH and a non-FH group of children (n 36) were included. The children with FH had previously received dietary counselling. The FH subjects were grouped as: 12–14 years (FH (12–14)) and 18–28 years (FH (18–28)). Dietary data were collected by SmartDiet, a short self-instructing questionnaire on diet and lifestyle where the total score forms the basis for an overall assessment of the diet. Clinical and biochemical data were retrieved from medical records. The SmartDiet scores were significantly improved in the FH (12–14) subjects compared with the non-FH subjects (SmartDiet score of 31 v. 28, respectively). More FH (12–14) subjects compared with non-FH children consumed low-fat milk (64 v. 18 %, respectively), low-fat cheese (29 v. 3%, respectively), used margarine with highly unsaturated fat (74 v. 14 %, respectively). In all, 68 % of the FH (12–14) subjects and 55 % of the non-FH children had fish for dinner twice or more per week. The FH (18–28) subjects showed the same pattern in dietary choices as the FH (12–14) children. In contrast to the choices of low-fat dietary items, 50 % of the FH (12–14) subjects consumed sweet spreads or sweet drinks twice or more per week compared with only 21 % in the non-FH group. In conclusion, ordinary out-patient dietary counselling of children with FH seems to have a long-lasting effect, as the diet of children and young adults with FH consisted of more products that are favourable with regard to the fatty acid composition of the diet.
doi:10.1017/jns.2013.27
PMCID: PMC4153102  PMID: 25191582
Familial hypercholesterolaemia; Children; Diet; Dietary fat sources; FH, familial hypercholesterolaemia; FH (12–14), FH subjects aged 12 to 14 years; FH (18–28), FH subjects aged 18 to 28 years
2.  Substitution of TAG oil with diacylglycerol oil in food items improves the predicted 10 years cardiovascular risk score in healthy, overweight subjects 
Dietary fat is normally in TAG form, but diacylglycerol (DAG) is a natural component of edible oils. Studies have shown that consumption of DAG results in metabolic characteristics that are distinct from those of TAG, which may be beneficial in preventing and managing obesity. The objective of the present study was to investigate if food items in which part of the TAG oil is replaced with DAG oil combined with high α-linolenic acid (ALA) content would influence metabolic markers. A 12-week double-blinded randomised controlled parallel-design study was conducted. The participants (n 23) were healthy, overweight men and women, aged 37–67 years, BMI 27–35 kg/m2, with waist circumference >94 cm (men) and >88 cm (women). The two groups received 20 g margarine, 11 g mayonnaise and 12 g oil per d, containing either high ALA and sn-1,3-DAG or high ALA and TAG. Substitution of TAG oil with DAG oil in food items for 12 weeks led to an improvement of the predicted 10 years cardiovascular risk score in overweight subjects by non-significantly improving markers of health such as total body fat percentage, trunk fat mass, alanine aminotransferase, systolic blood pressure, γ-glutamyl transferase, alkaline phosphatase and total fat-free mass. This may suggest that replacing TAG oil with DAG oil in healthy, overweight individuals may have beneficial metabolic effects.
doi:10.1017/jns.2012.18
PMCID: PMC4153080  PMID: 25191546
Diacylglycerol; TAG; Overweight human subjects; Liver markers; ALA, α-linolenic acid; ALAT, alanine aminotransferase; ALP, alkaline phosphatase; ASAT, aspartame aminotransferase; CRP, C-reactive protein; DAG, diacylglycerol; FFM, fat-free mass; γ-GT, γ-glutamyl transferase; HOMA-IR, homeostatic model assessment for insulin resistance; hsCRP, high-sensitivity CRP
3.  Comparison of bioavailability of krill oil versus fish oil and health effect 
Background
The aim of this review is to summarize the effects of krill oil (KO) or fish oil (FO) on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) incorporation in plasma phospholipids or membrane of red blood cells (RBCs) as shown in human and animal studies. Furthermore, we discuss the findings in relation to the possible different health effects, focusing on lipids, inflammatory markers, cardiovascular disease risk, and biological functions of these two sources of long-chain n-3 polyunsaturated fatty acids (PUFAs).
Methods
A literature search was conducted in PubMed in January 2015. In total, 113 articles were identified, but based on selection criteria, 14 original papers were included in the review.
Results
Studies on bioavailability of EPA and DHA from KO and FO in humans and animals are limited and the interpretation is difficult, as different amounts of EPA and DHA have been used, duration of intervention differs, and different study groups have been included. Two human studies – one postprandial study and one intervention study – used the same amount of EPA and DHA from KO or FO, and they both showed that the bioavailability of EPA and DHA from KO seems to be higher than that from FO. Limited effects of KO and FO on lipids and inflammatory markers in human and animal studies were reported. Gene expression data from animal studies showed that FO upregulated the cholesterol synthesis pathway, which was the opposite of the effect mediated by KO. KO also regulated far more metabolic pathways than FO, which may indicate different biological effects of KO and FO.
Conclusion
There seems to be a difference in bioavailability of EPA and DHA after intake of KO and FO, but more studies are needed before a firm conclusion can be made. It is also necessary to document the beneficial health effects of KO with more human studies and to elucidate if these effects differ from those after regular fish and FO intake.
doi:10.2147/VHRM.S85165
PMCID: PMC4559234  PMID: 26357480
human studies; animal studies; gene expression; cardiovascular disease; long-chain polyunsaturated fatty acids; inflammation; lipid metabolism
4.  Fructose content of low calorie diets: effect on cardiometabolic risk factors in obese women with polycystic ovarian syndrome: a randomized controlled trial 
Endocrine Connections  2015;4(3):144-154.
We aimed to examine whether a whole-grain crispbread (CB) low-fructose, low-calorie diet (LCD) might be superior to a traditional LCD based on fructose-rich liquid meal replacements (LMRs) with respect to improvement of various cardiometabolic risk factors and reproductive hormones. Parallel-group randomised controlled clinical trial. Morbidly obese women with polycystic ovarian syndrome (PCOS) were randomised to either an 8-week CB-LCD or LMR-LCD (900–1100 kcal/day, fructose 17 g/day or 85 g/day). A total of 51 women completed the study. Body weight, fat mass and waist circumference reduced by mean (s.d.) 10.0 (4.8) kg, 7.4 (4.2) kg and 8.5 (4.4) cm, with no significant differences between groups. Total-cholesterol, HDL-cholesterol and Apo-A1 were significantly reduced within both groups (all P values <0.01), with no significant between-group differences. The triacylglycerol and LDL-cholesterol levels were reduced within the LMR group only, with no significant between-group differences. Blood pressure and most measures of glucose metabolism improved significantly in both diet groups, with no significant between-group difference. Uric acid levels rose by 17.7 (46.4) and 30.6 (71.5) μmol/l in the CB and LMR group, respectively, with no significant difference between groups. Gastrointestinal discomfort was significantly and equally reduced in both intervention groups. Free testosterone index was reduced in both groups, with no significant difference between groups. Morbidly obese women with PCOS who underwent either an 8-week low or high-fructose LCD-diet had similar changes in various cardiometabolic risk factors and reproductive hormones. Registration at ClinicalTrials.gov: NCT00779571.
doi:10.1530/EC-15-0047
PMCID: PMC4488759  PMID: 26138702
low calorie diets; fructose; obesity; PCOS; weight loss; cardiometabolic risk-factors
5.  Effects of Exercise on Gene Expression of Inflammatory Markers in Human Peripheral Blood Cells: A Systematic Review 
Regular physical activity seems to be one of the most important contributors to prevent disease and promote health. Being physically active reduces the risk of developing chronic diseases such as cardiovascular disease, diabetes, and some types of cancers. The molecular mechanisms are however not fully elucidated. Depending on duration and intensity, exercise will cause disruption of muscle fibers triggering a temporary inflammatory response. This response may not only involve the muscle tissue, but also peripheral tissues such as white blood cells, which are important components of the immune system. The immune system plays a vital role in the development of atherosclerosis, thereby making white blood cells relevant to study when looking at molecular mechanisms induced by physical activity. In this review, we summarize the existing literature on exercise and gene expression in human white blood cells, and discuss these results in relation to inflammation and atherosclerosis.
doi:10.1007/s12170-015-0463-4
PMCID: PMC4439514  PMID: 26005511
Physical activity; Exercise; Gene expression; Inflammation; Atherosclerosis; Peripheral mononuclear blood cells; PBMCs; Leukocytes; Lymphocytes; Monocytes
6.  Marine n-3 Fatty Acids and Gene Expression in Peripheral Blood Mononuclear Cells 
Intake of marine n-3 fatty acids has been shown to have beneficial effects on cardiovascular disease. Gene expression analyses in peripheral blood mononuclear cells (PBMCs) are used to understand the underlying mechanisms of action of marine n-3 fatty acids. The aim of this review was to summarize the effects mediated by marine n-3 fatty acids on gene expression in PBMCs. A systematic literature search was conducted in PubMed in May 2014 and 14 papers were included. Targeted gene expression studies were reported in 9 papers and focused on genes involved in lipid metabolism and inflammation. Whole genome transcriptome analyses were conducted in 5 papers, and processes and pathways related to atherosclerotic plaque formation such as inflammation, oxidative stress response, cell cycle, cell adhesion, and apoptosis were modulated after fish oil supplementation. PBMC gene expression profiling has a potential to clarify further the molecular effects of fish oil consumption on human health.
doi:10.1007/s12170-014-0412-7
PMCID: PMC4176948  PMID: 25285180
Cardiovascular disease; Marine n-3 fatty acids; Dietary intervention study; Peripheral mononuclear cells; PBMCs; Inflammation; Lipid metabolism; Transcriptomics; Gene expression
7.  Subjects with Low Plasma HDL Cholesterol Levels Are Characterized by an Inflammatory and Oxidative Phenotype 
PLoS ONE  2013;8(11):e78241.
Background
Epidemiological studies have shown that low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of cardiovascular disease, but the mechanisms for the possible atheroprotective effects of HDL cholesterol have still not been fully clarified, in particular in relation to clinical studies.
Objective
To examine the inflammatory, anti-oxidative and metabolic phenotype of subjects with low plasma HDL cholesterol levels.
Methods and Results
Fifteen subjects with low HDL cholesterol levels (eleven males and four females) and 19 subjects with high HDL (three males and 16 females) were recruited. Low HDL cholesterol was defined as ≤10th age/sex specific percentile and high HDL-C was defined as ≥90 age/sex specific percentile. Inflammatory markers in circulation and PBMC gene expression of cholesterol efflux mediators were measured. Our main findings were: (i) subjects with low plasma HDL cholesterol levels were characterized by increased plasma levels of CRP, MMP-9, neopterin, CXCL16 and ICAM-1 as well as low plasma levels of adiponectin, suggesting an inflammatory phenotype; (ii) these individuals also had reduced paraoxonase (PON)1 activity in plasma and PON2 gene expression in peripheral blood mononuclear cells (PBMC) accompanied by increased plasma levels of oxidized LDL suggesting decreased anti-oxidative capacity; and (iii) PBMC from low HDL subjects also had decreased mRNA levels of ABCA1 and ABCG1, suggesting impaired reverse cholesterol transport.
Conclusion
Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype that could contribute to the increased risk of atherosclerotic disorders in these subjects with low HDL levels.
doi:10.1371/journal.pone.0078241
PMCID: PMC3823918  PMID: 24244297
8.  Increased Systemic and Local Interleukin 9 Levels in Patients with Carotid and Coronary Atherosclerosis 
PLoS ONE  2013;8(8):e72769.
Objective
Atherosclerosis is a chronic inflammatory disorder that involves a range of inflammatory mediators. Although interleukin (IL)-9 has been related to inflammation, there are at present no data on its role in atherosclerosis. Here we have examined IL-9 and IL-9 receptor (IL-9R) systemically and locally in patients with coronary and carotid atherosclerosis.
Methods
Plasma IL-9 was quantified by enzyme immunoassay and multiplex technology. IL-9 and IL-9R mRNA were quantified by real-time RT-PCR, and their localization within the lesion was assessed by immunohistochemistry.
Results
The main findings were: (i) Patients with carotid atherosclerosis had significantly raised IL-9 plasma levels compared with healthy controls (n = 28), with no differences between asymptomatic (n = 56) and symptomatic (n = 88) patients. (ii) On admission, patients with acute ST-elevation myocardial infarction (STEMI) (n = 42) had markedly raised IL-9 plasma levels which gradually declined during the first week post-MI. (iii) T cells and monocytes from patients with unstable angina (n = 17) had increased mRNA levels of IL-9 as compared with controls (n = 11). (iv) Carotid plaques (n = 68) showed increased mRNA levels of IL-9 and IL-9R compared to non-atherosclerotic vessels (n = 10). Co-localization to T cells (IL-9 and IL-9R) and macrophages (IL-9) were shown by immunohistochemistry. (v) IL-9 increased IL-17 release in peripheral blood mononuclear cells from patients with unstable angina (n = 5) and healthy controls (n = 5) with a particularly enhancing effect in cells from the patient group.
Conclusion
Our findings show increased IL-9 levels in different atherosclerotic disorders both systemically and within the lesion, suggesting a role for the IL-9/IL-9R axis in the atherosclerotic process, potentially involving IL-17 mediated mechanisms. However, the functional consequences of these findings should be further investigated.
doi:10.1371/journal.pone.0072769
PMCID: PMC3758349  PMID: 24023645
9.  Fish Oil Supplementation Alters the Plasma Lipidomic Profile and Increases Long-Chain PUFAs of Phospholipids and Triglycerides in Healthy Subjects 
PLoS ONE  2012;7(8):e42550.
Background
While beneficial health effects of fish and fish oil consumption are well documented, the incorporation of n-3 polyunsaturated fatty acids in plasma lipid classes is not completely understood. The aim of this study was to investigate the effect of fish oil supplementation on the plasma lipidomic profile in healthy subjects.
Methodology/Principal Findings
In a double-blinded randomized controlled parallel-group study, healthy subjects received capsules containing either 8 g/d of fish oil (FO) (1.6 g/d EPA+DHA) (n = 16) or 8 g/d of high oleic sunflower oil (HOSO) (n = 17) for seven weeks. During the first three weeks of intervention, the subjects completed a fully controlled diet period. BMI and total serum triglycerides, total-, LDL- and HDL-cholesterol were unchanged during the intervention period. Lipidomic analyses were performed using Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (QTOFMS), where 568 lipids were detected and 260 identified. Both t-tests and Multi-Block Partial Least Square Regression (MBPLSR) analysis were performed for analysing differences between the intervention groups. The intervention groups were well separated by the lipidomic data after three weeks of intervention. Several lipid classes such as phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, sphingomyelin, phosphatidylserine, phosphatidylglycerol, and triglycerides contributed strongly to this separation. Twenty-three lipids were significantly decreased (FDR<0.05) in the FO group after three weeks compared with the HOSO group, whereas fifty-one were increased including selected phospholipids and triglycerides of long-chain polyunsaturated fatty acids. After seven weeks of intervention the two intervention groups showed similar grouping.
Conclusions/Significance
In healthy subjects, fish oil supplementation alters lipid metabolism and increases the proportion of phospholipids and triglycerides containing long-chain polyunsaturated fatty acids. Whether the beneficial effects of fish oil supplementation may be explained by a remodeling of the plasma lipids into phospholipids and triglycerides of long-chain polyunsaturated fatty acids needs to be further investigated.
Trial Registration
ClinicalTrials.gov NCT01034423
doi:10.1371/journal.pone.0042550
PMCID: PMC3429454  PMID: 22952598
10.  Effect of marine n-3 fatty acids on circulating inflammatory markers in healthy subjects and subjects with cardiovascular risk factors 
Inflammation Research  2011;60(4):309-319.
Objective
The aim of the present paper was to review the literature in order to summarize the effects of marine n-3 fatty acids on circulating inflammatory markers among healthy subjects, subjects with high risk of developing cardiovascular disease (CVD) and in patients with CVD in human intervention studies.
Methods
A systematic literature search in PubMed was performed. Intervention studies describing the effects of marine n-3 fatty acids on circulating inflammatory markers in healthy subjects, subjects with high risk of CVD and patients with CVD were included. The following exclusion criteria were used: (1) interventions assessing inflammatory markers with ex vivo methods (2) interventions with children (3) articles describing animal or cell culture studies. Twenty-two articles were included. Additionally, 13 papers from their literature lists were included based on the same inclusion and exclusion criteria as the literature search.
Results and conclusion
Intervention studies with marine n-3 fatty acids administered from either fish or fish oil demonstrate different results on inflammatory markers. No firm conclusion can be drawn about the effect of marine n-3 fatty acids on circulating inflammatory markers in healthy individuals, individuals with high risk of developing CVD or individuals with CVD related diseases.
doi:10.1007/s00011-010-0302-5
PMCID: PMC3058501  PMID: 21229287
Omega-3 fatty acids; Atherosclerosis; Inflammation; Circulating inflammatory markers; PBMCs
11.  Suggestive evidence of associations between liver X receptor β polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe) 
BMC Medical Genetics  2010;11:144.
Background
The liver X receptors (LXR) α and β regulate lipid and carbohydrate homeostasis and inflammation. Lxrβ-/- mice are glucose intolerant and at the same time lean. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRβ and risk of type 2 diabetes mellitus (T2DM), obesity and related traits in 3 separate cohort studies.
Methods
Twenty LXRβ SNPs were identified by sequencing and genotyped in the HUNT2 adult nested case-control study for T2DM (n = 835 cases/1986 controls). Five tag-SNPs (rs17373080, rs2695121, rs56151148, rs2303044 and rs3219281), covering 99.3% of the entire common genetic variability of the LXRβ gene were identified and genotyped in the French MONICA adult study (n = 2318) and the European adolescent HELENA cross-sectional study (n = 1144). In silico and in vitro functionality studies were performed.
Results
We identified suggestive or significant associations between rs17373080 and the risk of (i) T2DM in HUNT2 (OR = 0.82, p = 0.03), (ii) obesity in MONICA (OR = 1.26, p = 0.05) and (iii) overweight/obesity in HELENA (OR = 1.59, p = 0.002). An intron 4 SNP (rs28514894, a perfect proxy for rs17373080) could potentially create binding sites for hepatic nuclear factor 4 alpha (HNF4α) and nuclear factor 1 (NF1). The C allele of rs28514894 was associated with ~1.25-fold higher human LXRβ basal promoter activity in vitro. However, no differences between alleles in terms of DNA binding and reporter gene transactivation by HNF4α or NF1 were observed.
Conclusions
Our results suggest that rs17373080 in LXRβ is associated with T2DM and obesity, maybe via altered LXRβ expression.
doi:10.1186/1471-2350-11-144
PMCID: PMC2958901  PMID: 20939869

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