Linda Granlund

Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARγ modulator

A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis9, trans11 (c 9,t11) and trans10, cis12 (t10,c12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the t10,c12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t10,c12 CLA affects lipid accumulation in adipocytes. We have shown that t10,c12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 μM and 25 μM, respectively. t10,c12 CLA fails to activate peroxisome proliferator-activated receptor γ (PPARγ) but selectively inhibits thiazolidinedione-induced PPARγ activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with t10,c12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPARγ as well as its target genes, fatty acid binding protein (aP2) and liver X receptor α (LXRα). Taken together, our results suggest that the trans10, cis12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPARγ modulator.

Plant sterols from rapeseed and tall oils: Effects on lipids, fat-soluble vitamins and plant sterol concentrations

BACKGROUND AND AIMS Data comparing the impact of different sources of plant sterols on CVD risk factors and antioxidant levels is scarce. We evaluated the effects of plant sterols from rapeseed and tall oils on serum lipids, lipoproteins, fat-soluble vitamins and plant sterol concentrations. METHODS AND RESULTS This was a double-blinded, randomized, crossover trial in which 59 hypercholesterolemic subjects consumed 25 g/day of margarine for 4 weeks separated by 1 week washout periods. The two experimental margarines provided 2g/day of plant sterols from rapeseed or tall oil. The control margarine had no added plant sterols. The control margarine reduced LDL cholesterol by 4.5% (95% CI 1.4, 7.6%). The tall and rapeseed sterol margarines additionally reduced LDL cholesterol by 9.0% (95% CI 5.5, 12.4%) and 8.2% (95% CI 5.2, 11.4%) and apolipoprotein B by 5.3% (95% CI 1.0, 9.6%) and 6.9% (95% CI 3.6, 10.2%), respectively. Lipid-adjusted beta-carotene concentrations were reduced by both sterol margarines (P<0.017). alpha-Tocopherol concentrations were reduced by the tall sterol compared to the rapeseed sterol margarine (P=0.001). Campesterol concentrations increased more markedly with the rapeseed sterol versus tall sterol margarine (P<0.001). The rapeseed sterol margarine increased while the tall sterol margarine decreased brassicasterol concentrations (P<0.001). CONCLUSIONS Plant sterols from tall and rapeseed oils reduce atherogenic lipids and lipoproteins similarly. The rapeseed sterol margarine may have more favorable effects on serum alpha-tocopherol concentrations.

Sulfur-substituted and α-methylated fatty acids as peroxisome proliferator-activated receptor activators

FA with varying chain lengths and an α-methyl group and/or a sulfur in the β-position were tested as peroxisome proliferator-activated receptor (PPAR)α,-δ(β), and-γ ligands by transient transfection in COS-1 cells using chimeric receptor expression plasmids, containing cDNAs encoding the ligand-binding domain of PPARα,-δ, and-γ. For PPARα, an increasing activation was found with increasing chain length of the sulfur-substituted FA up to C14-S acetic acid (tetradecylthioacetic acid=TTA). The derivatives were poor, and nonsignificant, activators of PPARδ. For PPARγ, activation increased with increasing chain length up to C16-S acetic acid. A methyl group was introduced in the α-position of palmitic acid, TTA, EPA, DHA, cis9,trans11CLA, and trans10,cis12 CLA. An increased activation of PPARα was obtained for the α-methyl derivatives compared with the unmethylated FA. This increase also resulted in increased expression of the two PPARα target genes acyl-CoA oxidase and liver FA-binding protein for α-methyl TTA, α-methyl EPA, and α-methyl DHA. Decreased or altered metabolism of these derivatives in the cells cannot be excluded. In conclusion, saturated FA with sulfur in the β-position and increasing carbon chain length from C9−S acetic acid to C14−S acetic acid have increasing effects as activators of PPARα and-γ in transfection assays. Furthermore, α-methyl FA derivatives of a saturated natural FA (palmitic acid), a sulfur-substituted FA (TTA), and PUFA (EPA, DHA, c9,t11 CLA, and t10,c12 CLA) are stronger PPARα activators than the unmethylated compounds.

Absorption of very-long-chain saturated fatty acids in totally hydrogenated fish oil

Partially hydrogenated fish oil (PHFO) contains a high amount of trans fatty acids (TFA). Total hydrogenation results in a minimal amount of TFA, but a high content of very-long-chain saturated fatty acids (VLCSFA). Absorption and metabolism of VLCSFA from totally hydrogenated fish oil (THFO) were studied in rats. Groups of eight rats were fed one of four diets containing 40 g soyabean oil (SBO)/kg (low-fat diet), 150 g SBO/kg (SBO diet), 40 g PHFO/kg (PHFO diet) or 40 g THFO/kg (THFO diet) for 4 weeks. A lower absorption coefficient of the fat content was found in the THFO group (61 %) compared with the other groups (PHFO 95 %, SBO 99 %, low fat 98 %; which was mainly due to reduced absorption of VLCSFA. A reduced weight gain was found for the THFO group compared with the other groups, but this was only significant when compared with the SBO group Faecal fat excretion (dry weight) was markedly increased in the THFO group (47 %), which was 2.4, 4.8 and 8.3 times higher compared with the groups fed PHFO, SBO and low-fat diets respectively. Serum total cholesterol was reduced for the PHFO and THFO groups whereas serum triacylglycerol was increased for the PHFO group compared with the other groups Animals fed THFO diet had an increased content of 20:0 and 22:0 in the serum triacylglycerol fraction whereas only 20:0 was increased in the serum phospholipid fraction The low absorption coefficient of THFO must be considered if this fat is to be used for consumption by animals or man.

Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: a double-blind, randomised controlled trial

The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD. However, the extent of food changes needed to achieve these effects is less explored. The aim of the present study was to investigate the effects of exchanging a few commercially available, regularly consumed key food items (e.g. spread on bread, fat for cooking, cheese, bread and cereals) with improved fat quality on total cholesterol, LDL-cholesterol and inflammatory markers in a double-blind randomised, controlled trial. In total, 115 moderately hypercholesterolaemic, non-statin-treated adults (25-70 years) were randomly assigned to an experimental diet group (Ex-diet group) or control diet group (C-diet group) for 8 weeks with commercially available food items with different fatty acid composition (replacing SFA with mostly n-6 PUFA). In the Ex-diet group, serum total cholesterol (P<0·001) and LDL-cholesterol (P<0·001) were reduced after 8 weeks, compared with the C-diet group. The difference in change between the two groups at the end of the study was -9 and -11 % in total cholesterol and LDL-cholesterol, respectively. No difference in change in plasma levels of inflammatory markers (high-sensitive C-reactive protein, IL-6, soluble TNF receptor 1 and interferon-γ) was observed between the groups. In conclusion, exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol, with no negative effect on levels of inflammatory markers. This shows that an exchange of a few commercially available food items was easy and manageable and led to clinically relevant cholesterol reduction, potentially affecting future CVD risk.

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.

A randomized controlled trial in Norwegian pharmacies on effects of risk alert and advice in people with elevated cardiovascular risk

We investigated if alerting subjects to elevated total cholesterol (TC), hemoglobin A1c (HbA1c) and blood pressure (BP) (cardiovascular disease (CVD) risk factors that are usually asymptomatic), and if providing advice would result in reduced risk. We conducted a multicenter (50 community pharmacies) parallel three-arm 8-week randomized controlled trial (RCT) with a 52-week follow-up visit. During six days of screening, TC, HDL- and LDL-cholesterol, triglycerides, HbA1c, BP and body mass index (BMI) were assessed in 1318 individuals. Of these, 582 with a measured and predefined elevated ad hoc CVD risk score were randomized to either Alert/advice (n = 198) (immediately alerted of their screening result and received healthy lifestyle-advice), Advice-only (n = 185) (received only advice) or Control (n = 199) (not alert, no advice). Changes in risk score and self-reported health-related behaviors (diet, alcohol, physical activity) were assessed in pharmacies after 8 weeks (N = 543; 93%). Although the primary analysis showed no significant difference between groups, the Control group had the largest reduction in risk score of 14%. The total (uncontrolled) sample (N = 543) reduced the risk score by 3.2% beyond estimated regression towards the mean and improved their health-related behaviors. Among the 65% (n = 377) who returned 52 weeks after baseline, 14% reported started using CVD preventive medication after the screening. The study demonstrated that while assessing risk factors and behaviors in pharmacies proved efficient and possibly led to a small risk decrease, alerting people to their screening result did not seem to be more effective than a self-directed approach. ClinicalTrials.gov identifier: NCT02223793.

Community pharmacies offer a potential high-yield and convenient arena for total cholesterol and CVD risk screening

Background Moderately elevated blood total cholesterol (TC), blood glucose (BG) and blood pressure (BP) are rarely symptomatic and as such many individuals remain untreated. We studied the yield of an in-pharmacy screening for identifying undetected high TC and strategies to reach those with absence of prior measurement of TC, BG and BP. Methods A cross-sectional TC screening study with complementary TC measurements and self-administered questionnaire was conducted for 1 week in each of 2012 and 2014 in 148 and 149 BootsTM Norge AS community pharmacies nationwide in Norway. Results Non-medicated adults (n = 21 090) with mean age 54.5 ± 16.0 were included. The study population resembled the Norwegian population in regards to body mass index, educational level, smokers and physical inactivity level, but with an overrepresentation of middle-aged women. Of 20 743 with available data, 11% (n = 2337) were unaware of their high TC ≥7.0 mmol/L, and an additional 8% were unaware of TC ≥6.2 mmol/L. More than 40% of the study sample had not measured TC or BG before. In order for future screenings to reach those who are less likely to have previously measured TC and BG, our results suggest that young, low-educated, overweight men and women should be targeted for TC measurement, whereas normal weigh men in all ages should be targeted for BG measurement. Conclusions In total 19% in an in-pharmacy screening were unaware of their elevated TC of ≥6.2 mmol/L. We also identified characteristics that could be used reach those who are less likely to have measured TC and BG.