Browsing by Subject "LIPOPROTEINS"

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  • Aminoff, Anna; Ledmyr, Helena; Thulin, Petra; Lundell, Kerstin; Nunez, Leyla; Strandhagen, Elisabeth; Murphy, Charlotte; Lidberg, Ulf; Westerbacka, Jukka; Franco-Cereceda, Anders; Liska, Jan; Nielsen, Lars Bo; Gafvels, Mats; Mannila, Maria Nastase; Hamsten, Anders; Yki-Järvinen, Hannele; Thelle, Dag; Eriksson, Per; Boren, Jan; Ehrenborg, Ewa (2010)
  • Saarinen, Harri Juhani; Sittiwet, Chaiyasit; Simonen, Piia; Nissinen, Markku J.; Stenman, Ulf-Håkan; Gylling, Helena; Palomäki, Ari (2018)
    We have earlier reported the reduction of total cholesterol low-density lipoprotein (LDL) cholesterol and oxidized LDL caused by short-term modification of diet with cold-pressed turnip rapeseed oil (CPTRO) instead of butter. The aim of this supplementary study was to determine whether the beneficial effects resulted from altered cholesterol metabolism during the intervention. Thirty-seven men with metabolic syndrome (MetS) completed an open, randomized and balanced crossover study. Subjects' usual diet was supplemented with either 37.5 g of butter or 35 mL of CPTRO for 6-8 weeks. Otherwise normal dietary habits and physical activity were maintained without major variations. Serum non-cholesterol sterols were assayed with gas-liquid chromatography and used as surrogate markers of whole-body cholesterol synthesis and absorption efficiency. Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration was analyzed with Quantikine ELISA Immunoassay. Serum cholesterol synthesis markers and serum cholestanol (absorption marker), all as ratios to cholesterol, did not differ between the periods. Serum campesterol and sitosterol ratios to cholesterol were significantly increased after the administration of CPTRO resulting from the increased intake of 217 mg/day of plant sterols in CPTRO. Serum PCSK9 concentration did not differ between CPTRO and butter periods. The reduction in serum cholesterol by 7.2% after consumption of rapeseed oil could not be explained by changes in cholesterol absorption, synthesis or PCSK9 metabolism in MetS.
  • Lahelma, Mari; Sädevirta, Sanja; Lallukka-Brück, Susanna; Sevastianova, Ksenia; Mustelin, Linda; Gylling, Helena; Rockette-Wagner, Bonny; Kriska, Andrea M.; Yki-Järvinen, Hannele (2019)
    Background: Weighted hula-hoops have gained popularity, but whether they indeed reshape the trunk or have beneficial metabolic effects in overweight subjects is unknown. Objectives: To determine effects of hula-hooping and walking matched for energy expenditure on android fat %, trunk muscle mass, and metabolic parameters in a randomized cross-over study. Design: We recruited 55 overweight nondiabetic subjects, who were randomized to hula-hooping (HULA) for 6 weeks using a 1.5-kg weighted hula-hoop followed by walking (WALK) for another 6 weeks or vice versa. The increments in energy expenditure were similar by HULA and WALK. Body composition (dual-energy X-ray absorptiometry) and metabolic parameters were measured at baseline and after HULA and WALK. The primary endpoint was the change in fat % in the android region. Results: A total of 53subjects (waist 92 +/- 1 cm, body mass index 28 +/- 1 kg/m(2)) completed the study. Body weight changed similarly (-0.6 +/- 0.2 vs. -0.5 +/- 0.2 kg, nonsignificant; HULA vs. WALK). During the intervention the subjects hula-hooped on average 12.8 +/- 0.5 min/day and walked 9,986 +/- 376 steps/day. The % fat in the android region decreased significantly by HULA but not by WALK (between-group change p <0.001). Trunk muscle mass increased more by HULA than by WALK (p <0.05). Waist circumference decreased more by HULA than by WALK (-3.1 +/- 0.3 cm vs. -0.7 +/- 0.4 cm, p <0.001; HULA vs. WALK). WALK but not HULA significantly lowered systolic blood pressure and increased HDL cholesterol while HULA significantly decreased LDL cholesterol. Conclusions: Hula-hooping with a weighted hula-hoop can be used to decrease abdominal fat % and increase trunk muscle mass in overweight subjects. Its LDL lowering effect resembles that described for resistance training. (c) 2019 The Author(s) Published by S. Karger AG, Basel
  • Miettinen, Helena E.; Rönö, Kristiina; Koivusalo, Saila; Stach-Lempinen, Beata; Pöyhönen-Alho, Maritta; Eriksson, Johan G.; Hiltunen, Timo P.; Gylling, Helena (2014)
  • Lassenius, Mariann I.; Ahola, Aila J.; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik; Lehto, Markku (2016)
    Bacterial lipopolysaccharides (LPS), potent inducers of inflammation, have been associated with chronic metabolic disturbances. Obesity is linked to dyslipidemia, increased body adiposity, and endotoxemia. We investigated the cross-sectional relationships between serum LPS activity and body adiposity as well as inflammation in 242 subjects with type 1 diabetes. Body fat distribution was measured by DXA and serum LPS activity by the limulus amebocyte lysate end-point assay. Since no interaction between visceral fat mass and sex was observed, data were pooled for the subsequent analyses. LPS was independently associated with visceral fat mass, when adjusted for traditional risk factors (age, sex, kidney status, hsCRP, insulin sensitivity). In the multivariate analysis, serum LPS activity and triglyceride concentrations had a joint effect on visceral fat mass, independent of these factors alone. A combination of high LPS and high hsCRP concentrations was also observed in those with the largest visceral fat mass. In conclusion, high serum LPS activity levels were associated with visceral fat mass in subjects with type 1 diabetes strengthening its role in the development of central obesity, inflammation and insulin resistance.
  • Matikainen, Niina; Söderlund, Sanni; Björnson, Elias; Pietiläinen, Kirsi; Hakkarainen, Antti; Lundbom, Nina; Taskinen, Marja-Riitta; Boren, Jan (2019)
    Aims Patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) exhibit considerable residual risk for cardiovascular disease (CVD). There is, therefore, increasing interest in targeting postprandial lipid metabolism and remnant cholesterol. Treatment with the glucagon-like peptide 1 (GLP-1) analogue liraglutide reduces CVD risk by mechanisms that remain unexplained in part. Here we investigated the effects of liraglutide intervention on ectopic fat depots, hepatic lipogenesis and fat oxidation, postprandial lipid metabolism and glycaemia in humans with type 2 diabetes. Methods The effect of liraglutide was investigated in 22 patients with adequately controlled type 2 diabetes. Patients were randomly allocated, in a single-blind fashion, to either liraglutide 1.8 mg or placebo once daily for 16 weeks. Because liraglutide is known to promote weight loss, the study included dietary counselling to achieve similar weight loss in the liraglutide and placebo groups. Cardiometabolic responses to a high-fat mixed meal were measured before and at the end of the liraglutide intervention. Results Weight loss at Week 16 was similar between the groups: -2.4 kg (-2.5%) in the liraglutide group and -2.1 kg (-2.2%) in the placebo group. HBA1c improved by 6.4 mmol/mol (0.6%) in the liraglutide group (P = 0.005). Liver fat decreased in both groups, by 31% in the liraglutide group and by 18% in the placebo group, but there were no significant changes in the rate of hepatic de novo lipogenesis or beta-hydroxybutyrate levels, a marker of fat oxidation. We observed significant postprandial decreases in triglycerides only in plasma, chylomicrons and VLDL, and remnant particle cholesterol after treatment in the liraglutide group. Fasting and postprandial apoCIII concentrations decreased after liraglutide intervention and these changes were closely related to reduced glycaemia. In relative importance analysis, approximately half of the changes in postprandial lipids were explained by reductions in apoCIII concentrations, whereas less than 10% of the variation in postprandial lipids was explained by reductions in weight, glycaemic control, liver fat or postprandial insulin responses. Conclusions Intervention with liraglutide for 16 weeks produces multiple improvements in cardiometabolic risk factors that were not seen in the placebo group, despite similar weight loss. Of particular importance was a marked reduction in postprandial atherogenic remnant particles. The underlying mechanism may be improved glycaemic control, which leads to reduced expression of apoCIII, a key regulator of hypertriglyceridaemia in hyperglycaemic patients.
  • Tikkanen, Emmi; Minicocci, Ilenia; Hällfors, Jenni; Di Costanzo, Alessia; D'Erasmo, Laura; Poggiogalle, Eleonora; Donini, Lorenzo Maria; Wurtz, Peter; Jauhiainen, Matti; Olkkonen, Vesa M.; Arca, Marcello (2019)
    Objective- Loss-of-function (LOF) variants in the ANGPTL3 (angiopoietin-like protein 3) have been associated with low levels of plasma lipoproteins and decreased coronary artery disease risk. We aimed to determine detailed metabolic effects of genetically induced ANGPTL3 deficiency in fasting and postprandial state. Approach and Results- We studied individuals carrying S17X LOF mutation in ANGPTL3 (6 homozygous and 32 heterozygous carriers) and 38 noncarriers. Nuclear magnetic resonance metabolomics was used to quantify 225 circulating metabolic measures. We compared metabolic differences between LOF carriers and noncarriers in fasting state and after a high-fat meal. In fasting, ANGPTL3 deficiency was characterized by similar extent of reductions in LDL (low-density lipoprotein) cholesterol (0.74 SD units lower concentration per LOF allele [95% CI, 0.42-1.06]) as observed for many TRL (triglyceride-rich lipoprotein) measures, including VLDL (very-low-density lipoprotein) cholesterol (0.75 [95% CI, 0.45-1.05]). Within most lipoprotein subclasses, absolute levels of cholesterol were decreased more than triglycerides, resulting in the relative proportion of cholesterol being reduced within TRLs and their remnants. Further, beta-hydroxybutyrate was elevated (0.55 [95% CI, 0.21-0.89]). Homozygous ANGPTL3 LOF carriers showed essentially no postprandial increase in TRLs and fatty acids, without evidence for adverse compensatory metabolic effects. Conclusions- In addition to overall triglyceride- and LDL cholesterol-lowering effects, ANGPTL3 deficiency results in reduction of cholesterol proportion within TRLs and their remnants. Further, ANGPTL3 LOF carriers had elevated ketone body production, suggesting enhanced hepatic fatty acid beta-oxidation. The detailed metabolic profile in human knockouts of ANGPTL3 reinforces inactivation of ANGPTL3 as a promising therapeutic target for decreasing cardiovascular risk.
  • Ellul, Susan; Wake, Melissa; Clifford, Susan A.; Lange, Katherine; Würtz, Peter; Juonala, Markus; Dwyer, Terence; Carlin, John B.; Burgner, David P.; Saffery, Richard (2019)
    Objectives Nuclear magnetic resonance (NMR) metabolomics is high throughput and cost-effective, with the potential to improve the understanding of disease and risk. We examine the circulating metabolic profile by quantitative NMR metabolomics of a sample of Australian 11-12 year olds children and their parents, describe differences by age and sex, and explore the correlation of metabolites in parent-child dyads. Design The population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children. Setting Blood samples collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns; February 2015-March 2016. Participants 1180 children and 1325 parents provided a blood sample and had metabolomics data available. This included 1133 parent-child dyads (518 mother-daughter, 469 mother-son, 68 father-daughter and 78 father-son). Outcome measures 228 metabolic measures were obtained for each participant. We focused on 74 biomarkers including amino acid species, lipoprotein subclass measures, lipids, fatty acids, measures related to fatty acid saturation, and composite markers of inflammation and energy homeostasis. Results We identified differences in the concentration of specific metabolites between childhood and adulthood and in metabolic profiles in children and adults by sex. In general, metabolite concentrations were higher in adults than children and sex differences were larger in adults than in children. Positive correlations were observed for the majority of metabolites including isoleucine (CC 0.33, 95% CI 0.27 to 0.38), total cholesterol (CC 0.30, 95% CI 0.24 to 0.35) and omega 6 fatty acids (CC 0.28, 95% CI 0.23 to 0.34) in parent-child comparisons. Conclusions We describe the serum metabolite profiles from mid-childhood and adulthood in a population-based sample, together with a parent-child concordance. Differences in profiles by age and sex were observed. These data will be informative for investigation of the childhood origins of adult non-communicable diseases and for comparative studies in other populations.
  • Lassenius, Mariann I.; Makinen, Ville-Petteri; Fogarty, Christopher; Peraneva, Lina; Jauhiainen, Matti; Pussinen, Pirkko J.; Taskinen, Marja-Riitta; Kirveskari, Juha; Vaarala, Outi; Nieminen, Janne K.; Horkko, Sohvi; Kangas, Antti J.; Soininen, Pasi; Ala-Korpela, Mika; Gordin, Daniel; Ahola, Aila J.; Forsblom, Carol; Groop, Per Henrik; Lehto, Markku; FinnDiane Study Grp (2014)
  • Liangsupree, Thanaporn; Multia, Evgen; Saarinen, Jukka; Ruiz-Jimenez, Jose; Kemell, Marianna; Riekkola, Marja-Liisa (2022)
    Raman spectroscopy together with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GCxGC-TOFMS) was employed to characterize exomere- (<50 nm) and exosome-sized (50-80 nm) EVs isolated from human plasma by the novel on-line immunoaffinity chromatography - asymmetric flow field-flow fractionation method. CD9(+), CD63(+), and CD81(+) EVs were selected to represent general EV subpopulations secreted into plasma, while CD61(+) EVs represented the specific EV subset derived from platelets. Raman spectroscopy could distinguish EVs from non-EV particles, including apolipoprotein B-100-containing lipoproteins, signifying its potential in EV purity assessment. Moreover, platelet-derived (CD61(+)) EVs of both exomere and exosome sizes were discriminated from other EV subpopulations due to different biochemical compositions. Further investigations demonstrated composition differences between exomere- and exosome-sized EVs, confirming the applicability of Raman spectroscopy in distinguishing EVs, not only from different origins but also sizes. In addition, fatty acids that act as building blocks for lipids and membranes in EVs were studied by GCxGC-TOF-MS. The results achieved highlighted differences in EV fatty acid compositions in both esterified (membrane lipids) and non-esterified (free fatty acids) fractions, indicating possible differences in membrane structures, biological functions, and roles in cell-to-cell communications of EV subpopulations.
  • Liangsupree, Thanaporn; Multia, Evgen; Metso, Jari; Jauhiainen, Matti; Forssen, Patrik; Fornstedt, Torgny; Öörni, Katariina; Podgornik, Ales; Riekkola, Marja-Liisa (2019)
    Low-density lipoprotein (LDL) is considered the major risk factor for the development of atherosclerotic cardiovascular diseases (ASCVDs). A novel and rapid method for the isolation of LDL from human plasma was developed utilising affinity chromatography with monolithic stationary supports. The isolation method consisted of two polymeric monolithic disk columns, one immobilized with chondroitin-6-sulfate (C6S) and the other with apolipoprotein B-100 monoclonal antibody (anti-apoB-100 mAb). The first disk with C6S was targeted to remove chylomicrons, very-low-density lipoprotein (VLDL) particles, and their remnants including intermediate-density lipoprotein (IDL) particles, thus allowing the remaining major lipoprotein species, i.e. LDL, lipoprotein(a) (Lp(a)), and high-density lipoprotein (HDL) to flow to the anti-apoB-100 disk. The second disk captured LDL particles via the anti-apoB-100 mAb attached on the disk surface in a highly specific manner, permitting the selective LDL isolation. The success of LDL isolation was confirmed by different techniques including quartz crystal microbalance. In addition, the method developed gave comparable results with ultracentrifugation, conventionally used as a standard method. The reliable results achieved together with a short isolation time (less than 30 min) suggest the method to be suitable for clinically relevant LDL functional assays.
  • Forssen, Patrik; Multia, Evgen; Samuelsson, Jorgen; Andersson, Marie; Aastrup, Teodor; Altun, Samuel; Wallinder, Daniel; Wallbing, Linus; Liangsupree, Thanaporn; Riekkola, Marja-Liisa; Fornstedt, Torgny (2018)
    When using biosensors, analyte biomolecules of several different concentrations are percolated over a chip with immobilized ligand molecules that form complexes with analytes. However, in many cases of biological interest, e.g., in antibody interactions, complex formation steady-state is not reached. The data measured are so-called sensorgram, one for each analyte concentration, with total complex concentration vs time. Here we present a new four-step strategy for more reliable processing of this complex kinetic binding data and compare it with the standard global fitting procedure. In our strategy, we first calculate a dissociation graph to reveal if there are any heterogeneous interactions. Thereafter, a new numerical algorithm, AIDA, is used to get the number of different complex formation reactions for each analyte concentration level. This information is then used to estimate the corresponding complex formation rate constants by fitting to the measured sensorgram one by one. Finally, all estimated rate constants are plotted and clustered, where each cluster represents a complex formation. Synthetic and experimental data obtained from three different QCM biosensor experimental systems having fast (close to steady-state), moderate, and slow kinetics (far from steady-state) were evaluated using the four-step strategy and standard global fitting. The new strategy allowed us to more reliably estimate the number of different complex formations, especially for cases of complex and slow dissociation kinetics. Moreover, the new strategy proved to be more robust as it enables one to handle system drift, i.e., data from biosensor chips that deteriorate over time.
  • Ahola, Aila J.; Harjutsalo, Valma; Thorn, Lena; Freese, Riitta; Forsblom, Carol; Mäkimattila, Sari; Groop, Per-Henrik; FinnDiane Study Grp (2017)
    Diet is a major modifiable lifestyle factor that may affect the components of the metabolic syndrome. We aimed to investigate the association between relative proportions of macronutrients and the components of the metabolic syndrome in a population of individuals with type 1 diabetes. In all, 791 individuals without nephropathy, with plausible energy intake and known metabolic syndrome status, taking part in the Finnish Diabetic Nephropathy Study were included in the analyses. Dietary data were collected with a diet record. The association between the relative macronutrient intake and the outcome variables were analysed using multivariable nutrient density substitution models. The relative proportions of dietary macronutrients or fatty acids were not associated with the presence of the metabolic syndrome. In men, however, favouring carbohydrates over fats was associated with lower odds of the waist component, whereas favouring either carbohydrates or fats over proteins was associated with lower odds of the blood pressure component of the metabolic syndrome. In women, substituting carbohydrates for fats was associated with lower HDL-cholesterol concentration. Substituting carbohydrates or fats for alcohol or protein was, in men, associated with lower systolic blood pressure. To conclude, the relative distribution of macronutrients may have some relevance for the metabolic syndrome.
  • Velagapudi, Vidya R.; Hezaveh, Rahil; Reigstad, Christopher S.; Gopalacharyulu, Peddinti; Yetukuri, Laxman; Islam, Sama; Felin, Jenny; Perkins, Rosie; Boren, Jan; Oresic, Matej; Backhed, Fredrik (2010)
  • Hemilä, Harri (1992)
    There has been a long-lasting controversy about whether vitamin C has any significant effect on plasma cholesterol levels in human beings. Some early Russian studies suggested that vitamin C may decrease elevated cholesterol levels, and so the vitamin was used to some extent in the treatment of hypercholesterolemia (for review see Reference 1). However, the studies were not well controlled, and duplications have yielded conflicting results. Nevertheless, animal studies have consistently found that vitamin C has substantial effects on cholesterol metabolism. The purpose of this review is to analyze the published intervention studies in order to identify the factors that may have resulted in the discordance in the results. Several of the studies have used subjects with initially low cholesterol levels. Such studies do not test the hypothesis that a low level of the vitamin may decrease the rate of cholesterol catabolism, and thereby enhance hypercholesterolemia in some people. Accordingly, studies with hypercholesterolemic subjects are more relevant for testing this hypothesis. Most of the studies in the latter group have reported a significant decrease in the cholesterol level with vitamin C supplementation. Furthermore, such results indicate that in certain people low vitamin C status may be one of the factors that lead to the elevation of cholesterol levels.