Linda Granlund

University of Oslo, Oslo, Oslo, Norway

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Publications (15)45.09 Total impact

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    ABSTRACT: OBJECTIVE: Phytosterols are recommended in combination with diet therapy to reduce elevated LDL-cholesterol level. Meta-analyses indicate a 10% reduction in LDL-cholesterol from intake of approximately 2 g phytosterols/d incorporated into fat-based foods. However, the cholesterol lowering effect from capsules containing phytosterols is less documented. The pre-specified primary endpoint of the present study was to investigate the effect of capsules with phytosterols on circulating LDL-cholesterol in patients with mild to moderate hypercholesterolemia. METHODS: In a double-blinded, randomized, placebo-controlled crossover study, 41 men and women were randomized into two four-weeks intervention periods with softgel capsules containing either phytosterols (2.0 g/d) or sunflower oil. There was a three-weeks washout period between the intervention periods. RESULTS: No significant difference in total- or LDL-cholesterol between the phytosterol and the placebo period were observed after four weeks intervention (0.0 mmol/L (95%CI: -0.3 to 0.2), P = 0.74 and -0.1 mmol/L (95%CI: -0.3 to 0.1), P = 0.32, respectively). CONCLUSION: Daily intake of capsules containing 2 g phytosterols did not reduce total- or LDL-cholesterol significantly in a highly relevant target group for the use of phytosterol products. The present results may emphasize the importance of choosing a suitable dosage-delivery system in order to achieve optimal cholesterol lowering effect. The study was registered at www.clinicaltrials.gov, IDno:NCT00485095.
    Atherosclerosis 03/2013; · 3.71 Impact Factor
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    ABSTRACT: Obesity (BMI ≥30 kg/m(2)) increases the risk of developing lifestyle-related diseases. A subgroup of obese individuals has been described as "metabolically healthy, but obese" (MHO). In contrast to at-risk obese (ARO), the MHO phenotype is defined by a favourable lipid profile and a normal or only slightly affected insulin sensitivity, despite the same amount of body fat. The objective was to characterize the metabolic phenotype of MHO subjects. We screened a variety of genes involved in lipid metabolism and inflammation in peripheral blood mononuclear cells (PBMC). Obese subjects (men and women; 18-70 years) with BMI ≥30 kg/m(2) were characterized as MHO (n = 9) or as ARO (n = 10). In addition, eleven healthy, normal weight subjects characterized as healthy by the same criteria as described for the MHO subjects were included. We found that with similar weight, total fat mass and fat mass distribution, the ARO subjects have increased plasma levels of gamma-glutamyl transpeptidase and free fatty acids. This group also has altered expression levels of a number of genes linked to lipid metabolism in PBMC with reduced gene expression levels of uncoupling protein 2, hormone-sensitive lipase and peroxisome proliferator-activated receptor δ compared with MHO subjects. The present metabolic differences between subgroups of obese subjects may contribute to explain some of the underlying mechanisms causing the increased risk of disease among ARO subjects compared with MHO subjects.
    Genes & Nutrition 01/2013; · 3.33 Impact Factor
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    ABSTRACT: 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.
    Journal of Nutritional Science. 01/2012; 1.
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    ABSTRACT: The aim of the present study was to examine the effect of a single high-fat meal with different fat quality on circulating inflammatory markers and gene expression in peripheral blood mononuclear cells (PBMC) to elucidate the role of fat quality on postprandial inflammation. A postprandial study with fourteen healthy females consuming three test meals with different fat quality was performed. Test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analysed. The test meal consisted of three cakes enriched with coconut fat (43 % energy as saturated fat and 1 % energy as α-linolenic acid (ALA)), linseed oil (14 % energy as ALA and 30 % energy as saturated fat) and cod liver oil (5 % energy as EPA and DHA and 5 % energy as ALA in addition to 31 % energy as saturated fat). In addition, ex vivo PBMC experiments were performed in eight healthy subjects investigating the effects of EPA and ALA on release and gene expression of inflammatory markers. The IL-8 mRNA level was significantly increased after intake of the cod liver oil cake at 6 h compared with fasting level, which was significantly different from the effect observed after the intake of linseed cake. In contrast, no effect was seen on circulating level of IL-8. In addition, ALA and EPA were shown to elicit different effects on the release and mRNA expression levels of inflammatory markers in PBMC cultured ex vivo, with EPA having the most prominent pro-inflammatory potential.
    The British journal of nutrition 06/2011; 106(12):1826-35. · 3.45 Impact Factor
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    ABSTRACT: Aging is associated with alterations in the intestinal microbiota and with immunosenescence. Probiotics have the potential to modify a selected part of the intestinal microbiota as well as improve immune functions and may, therefore, be particularly beneficial to elderly consumers. In this randomized, controlled cross-over clinical trial, we assessed the effects of a probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM on the intestinal microbiota and fecal immune markers of 31 elderly volunteers and compared these effects with the administration of the same cheese without probiotics. The probiotic cheese was found to increase the number of L. rhamnosus and L. acidophilus NCFM in the feces, suggesting the survival of the strains during the gastrointestinal transit. Importantly, probiotic cheese administration was associated with a trend towards lower counts of Clostridium difficile in the elderly, as compared with the run-in period with the plain cheese. The effect was statistically significant in the subpopulation of the elderly who harbored C. difficile at the start of the study. The probiotic cheese was not found to significantly alter the levels of the major microbial groups, suggesting that the microbial changes conferred by the probiotic cheese were limited to specific bacterial groups. Despite that the administration of the probiotic cheese to the study population has earlier been shown to significantly improve the innate immunity of the elders, we did not observe measurable changes in the fecal immune IgA concentrations. No increase in fecal calprotectin and β-defensin concentrations suggests that the probiotic treatment did not affect intestinal inflammatory markers. In conclusion, the administration of probiotic cheese containing L. rhamnosus HN001 and L. acidophilus NCFM, was associated with specific changes in the intestinal microbiota, mainly affecting specific subpopulations of intestinal lactobacilli and C. difficile, but did not have significant effects on the major microbial groups or the fecal immune markers.
    Age 01/2011; 34(1):133-43. · 6.28 Impact Factor
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    ABSTRACT: Oral intake of specific probiotics has been reported to enhance the immunity of the elderly. Earlier studies have used milk or yoghurt as a probiotic carrier. We chose a commercial probiotic cheese to evaluate its potential as a probiotic food. Thirty-one healthy elderly volunteers (21 female, 10 male) aged from 72 to 103 (median 86) consumed a commercial probiotic cheese containing approximately 10(9) CFU day(-1) of Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM. The 4-week probiotic intervention was preceded by a 2-week consumption of probiotic-free cheese (run-in) and followed by a 4-week wash-out period with the same control cheese. The cytotoxicity of peripheral blood mononuclear cells (PBMCs), the relative numbers of natural killer (NK) and NKT cells in the total PBMCs, and phagocytic activity were assessed. Consumption of the probiotic cheese significantly increased the cytotoxicity of NK cells. A significant increase in phagocytosis was observed for both the control and the probiotic cheese. Cheese was found to be an effective carrier for the study of probiotics, and daily consumption of the probiotic enhanced parameters of innate immunity in elderly volunteers. It remains to be determined whether this enhancement correlates with a beneficial effect on the health of the elderly population.
    FEMS Immunology & Medical Microbiology 02/2010; 59(1):53-9. · 2.68 Impact Factor
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    ABSTRACT: 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. 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). 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.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 09/2009; 20(4):258-65. · 3.52 Impact Factor
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    ABSTRACT: In this study, probiotics Lactobacillus acidophilus NCFM and Lactobacillus rhamnosus HN001 in cheese were studied using models simulating the human gastrointestinal tract with the aim of investigating whether the cheese matrix affected the survival and metabolic properties of these probiotic strains. Probiotics in cheese survived in the simulated upper gastrointestinal tract model, and numbers of L. acidophilus, L. rhamnosus and total lactobacilli were increased in the colonic fermentation simulations of the probiotic cheese when compared with the non-probiotic cheese used as a control. The cheese matrix also beneficially affected cyclooxygenase-gene expression of colonocytes in a cell culture model. Freeze-dried probiotics, which were also analysed in the colonic simulator, showed similar changes in Lactobacillus numbers, although gave a stronger increase and also affected other microbial groups. These results indicate that the probiotic microbes in cheese survive in the gastrointestinal tract and that the cheese matrix does not seem to affect the probiotic survival.
    International Dairy Journal. 01/2009;
  • Linda Granlund, Jan I Pedersen, Hilde I Nebb
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    ABSTRACT: Conjugated linoleic acids (CLAs) are a group of polyunsaturated fatty acids found in ruminant products, where the predominant isomers are cis9, trans11 (c9,t11) and trans10, cis12 (t10,c12) CLA. We have previously shown that t10,c12 CLA prevents lipid accumulation in mature adipocytes in part by acting as a peroxisome proliferator-activated receptor gamma (PPAR gamma) modulator. The objective of this study was to further establish the molecular mechanisms underlying the attenuating effect on lipid accumulation by t10,c12 CLA, with focus on time point and duration of treatment during adipogenesis. We have shown that t10,c12 CLA treatment has its most attenuating effect early (day (D) 0-6) during differentiation. Treatment during this period is sufficient to prevent lipid accumulation in mature adipocytes. The adipogenic marker genes PPAR gamma and CCAAT/enhancer binding protein alpha (C/EBP alpha) are both down-regulated after treatment within the period from D0-6, while additional treatment also down-regulates the expression of sterol regulatory element binding protein-1c (SREBP-1c), liver X receptor alpha (LXR alpha), fatty acid binding protein (aP2), fatty acid translocase (CD36) and insulin-sensitive glucose transporter 4 (GLUT4). These effects of t10,c12 CLA reflect the subsequent attenuation of lipid accumulation observed in mature adipocytes. Interestingly, the early B-cell factor (O/E-1), which is known to promote adipogenesis and to be involved in control of genes important for terminal adipocyte differentiation, is unaffected by treatment of t10,c12 CLA. Taken together, our data indicate that inhibition of lipid accumulation induced by t10,c12 CLA treatment during adipocyte differentiation is associated with a tight regulatory cross-talk between early (PPAR gamma and C/EBP alpha) and late (LXR alpha, aP2 and CD36) adipogenic marker genes.
    Biochimica et Biophysica Acta 03/2005; 1687(1-3):11-22. · 4.66 Impact Factor
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    ABSTRACT: Conjugated linoleic acids (CLAs), tetradecylthioacetic acid (TTA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are all shown to differently affect lipid homeostasis. Additionally, previous studies have shown that introducing a methyl group in the molecule potentiates the hypolipidemic effect of EPA. The objective of this study was to determine how cis9,trans11 CLA, trans10,cis12 CLA, TTA, EPA and DHA affect lipid accumulation in 3T3-L1 adipocytes and in cultured primary rat hepatocytes, and to what extent changes in cis/trans configuration or introducing a methyl group in the molecules influence their way of affecting lipid accumulation in these cells. Our results show that trans10,cis12 CLA is highly specific in preventing lipid accumulation in adipocytes, and that small structural changes in the molecule (changing to trans/trans or introducing an alpha-methyl group) totally abolish this effect and up-regulate the expression levels of adipogenic marker genes towards control levels. Furthermore, all the fatty acids increased hepatic lipid accumulation, whereas the lipid content was normalized after adding an alpha-methyl group into the molecules. Taken together, our data demonstrate that the various fatty acids are highly specialized molecules, and that small structural changes markedly alter their way of affecting lipid accumulation in adipocytes and hepatocytes.
    Biochimica et Biophysica Acta 03/2005; 1687(1-3):23-30. · 4.66 Impact Factor
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    ABSTRACT: FA with varying chain lengths and an alpha-methyl group and/or a sulfur in the beta-position were tested as peroxisome proliferator-activated receptor (PPAR)alpha, -delta(beta), and -gamma ligands by transient transfection in COS-1 cells using chimeric receptor expression plasmids, containing cDNAs encoding the ligand-binding domain of PPARalpha, -delta, and -gamma. For PPARalpha, 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 PPARdelta. For PPARgamma, activation increased with increasing chain length up to C16-S acetic acid. A methyl group was introduced in the alpha-position of palmitic acid, TTA, EPA, DHA, cis9,trans11 CLA, and trans10,cis12 CLA. An increased activation of PPARalpha was obtained for the alpha-methyl derivatives compared with the unmethylated FA. This increase also resulted in increased expression of the two PPARalpha target genes acyl-CoA oxidase and liver FA-binding protein for alpha-methyl TTA, alpha-methyl EPA, and alpha-methyl DHA. Decreased or altered metabolism of these derivatives in the cells cannot be excluded. In conclusion, saturated FA with sulfur in the beta-position and increasing carbon chain length from C9-S acetic acid to C14-S acetic acid have increasing effects as activators of PPARalpha and -gamma in transfection assays. Furthermore, alpha-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 PPARalpha activators than the unmethylated compounds.
    Lipids 02/2005; 40(1):49-57. · 2.56 Impact Factor
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    ABSTRACT: 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.
    Lipids 01/2005; 40(1):49-57. · 2.56 Impact Factor
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    ABSTRACT: 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 microM and 25 microM, respectively. t10,c12 CLA fails to activate peroxisome proliferator-activated receptor gamma (PPARgamma) but selectively inhibits thiazolidinedione-induced PPARgamma 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 PPARgamma as well as its target genes, fatty acid binding protein (aP2) and liver X receptor alpha (LXRalpha). Taken together, our results suggest that the trans10, cis12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPARgamma modulator.
    The Journal of Lipid Research 09/2003; 44(8):1441-52. · 4.39 Impact Factor
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    ABSTRACT: 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.
    British Journal Of Nutrition 12/2000; 84(5):681-8. · 3.30 Impact Factor
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    ABSTRACT: A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis 9, trans 11 ( c 9, t 11) and trans 10, cis 12 ( t 10, c 12) 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 t 10, c 12 isomer hav- ing the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t 10, c 12 CLA affects lipid accumulation in adipocytes. We have shown that t 10, c 12 CLA prevents lipid accumulation in hu- man and mouse adipocytes at concentrations as low as 5 � M and 25 � M, respectively. t 10, c 12 CLA fails to activate perox- isome proliferator-activated receptor � (PPAR � ) but selec- tively inhibits thiazolidinedione-induced PPARactivation in 3T3-L1 adipocytes. Treatment of mature adipocytes with t 10, c 12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPARas well as its target genes, fatty acid binding protein (aP2) and liver X receptor � (LXR � ). Taken together, our results suggest that the trans 10, cis 12 CLA isomer prevents lipid accumula- tion in adipocytes by acting as a PPARmodulator. — Granlund, L., L. K. Juvet, J. I. Pedersen, and H. I. Nebb. Trans 10, cis 12-conjugated linoleic acid prevents triacylglyc- erol accumulation in adipocytes by acting as a PPARmod- ulator. J. Lipid Res. 2003. 44: 1441-1452.