173 results on '"Söderlund, Sanni"'
Search Results
2. Genetic architecture of human plasma lipidome and its link to cardiovascular disease.
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Tabassum, Rubina, Rämö, Joel T, Ripatti, Pietari, Koskela, Jukka T, Kurki, Mitja, Karjalainen, Juha, Palta, Priit, Hassan, Shabbeer, Nunez-Fontarnau, Javier, Kiiskinen, Tuomo TJ, Söderlund, Sanni, Matikainen, Niina, Gerl, Mathias J, Surma, Michal A, Klose, Christian, Stitziel, Nathan O, Laivuori, Hannele, Havulinna, Aki S, Service, Susan K, Salomaa, Veikko, Pirinen, Matti, FinnGen Project, Jauhiainen, Matti, Daly, Mark J, Freimer, Nelson B, Palotie, Aarno, Taskinen, Marja-Riitta, Simons, Kai, and Ripatti, Samuli
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FinnGen Project ,Plasma ,Humans ,Cardiovascular Diseases ,Lipids ,Genome-Wide Association Study ,Lipidomics - Abstract
Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P
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- 2019
3. Coronary Artery Disease Risk and Lipidomic Profiles Are Similar in Hyperlipidemias With Family History and Population‐Ascertained Hyperlipidemias
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Rämö, Joel T, Ripatti, Pietari, Tabassum, Rubina, Söderlund, Sanni, Matikainen, Niina, Gerl, Mathias J, Klose, Christian, Surma, Michal A, Stitziel, Nathan O, Havulinna, Aki S, Pirinen, Matti, Salomaa, Veikko, Freimer, Nelson B, Jauhiainen, Matti, Palotie, Aarno, Taskinen, Marja‐Riitta, Simons, Kai, and Ripatti, Samuli
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Atherosclerosis ,Digestive Diseases ,Heart Disease ,Cardiovascular ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Cholesterol ,LDL ,Coronary Artery Disease ,Family ,Female ,Finland ,Humans ,Hypercholesterolemia ,Hyperlipidemias ,Hypertriglyceridemia ,Lipidomics ,Male ,Medical History Taking ,Middle Aged ,Proportional Hazards Models ,Triglycerides ,coronary artery disease ,family study ,high-risk populations ,hypercholesterolemia ,hypertriglyceridemia ,lipids and lipoproteins ,high‐risk populations ,Cardiorespiratory Medicine and Haematology - Abstract
Background We asked whether, after excluding familial hypercholesterolemia, individuals with high low-density lipoprotein cholesterol ( LDL -C) or triacylglyceride levels and a family history of the same hyperlipidemia have greater coronary artery disease risk or different lipidomic profiles compared with population-based hyperlipidemias. Methods and Results We determined incident coronary artery disease risk for 755 members of 66 hyperlipidemic families (≥2 first-degree relatives with similar hyperlipidemia) and 19 644 Finnish FINRISK population study participants. We quantified 151 circulating lipid species from 550 members of 73 hyperlipidemic families and 897 FINRISK participants using mass spectrometric shotgun lipidomics. Familial hypercholesterolemia was excluded using functional LDL receptor testing and genotyping. Hyperlipidemias ( LDL -C or triacylglycerides >90th population percentile) associated with increased coronary artery disease risk in meta-analysis of the hyperlipidemic families and the population cohort (high LDL -C: hazard ratio, 1.74 [95% CI, 1.48-2.04]; high triacylglycerides: hazard ratio, 1.38 [95% CI, 1.09-1.74]). Risk estimates were similar in the family and population cohorts also after adjusting for lipid-lowering medication. In lipidomic profiling, high LDL -C associated with 108 lipid species, and high triacylglycerides associated with 131 lipid species in either cohort (at 5% false discovery rate; P-value range 0.038-2.3×10-56). Lipidomic profiles were highly similar for hyperlipidemic individuals in the families and the population ( LDL -C: r=0.80; triacylglycerides: r=0.96; no lipid species deviated between the cohorts). Conclusions Hyperlipidemias with family history conferred similar coronary artery disease risk as population-based hyperlipidemias. We identified distinct lipidomic profiles associated with high LDL -C and triacylglycerides. Lipidomic profiles were similar between hyperlipidemias with family history and population-ascertained hyperlipidemias, providing evidence of similar and overlapping underlying mechanisms.
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- 2019
4. Family-specific aggregation of lipid GWAS variants confers the susceptibility to familial hypercholesterolemia in a large Austrian family
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Nikkola, Elina, Ko, Arthur, Alvarez, Marcus, Cantor, Rita M, Garske, Kristina, Kim, Elliot, Gee, Stephanie, Rodriguez, Alejandra, Muxel, Reinhard, Matikainen, Niina, Söderlund, Sanni, Motazacker, Mahdi M, Borén, Jan, Lamina, Claudia, Kronenberg, Florian, Schneider, Wolfgang J, Palotie, Aarno, Laakso, Markku, Taskinen, Marja-Riitta, and Pajukanta, Päivi
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Digestive Diseases ,Human Genome ,Prevention ,Genetics ,Heart Disease ,Cardiovascular ,Atherosclerosis ,Aetiology ,2.1 Biological and endogenous factors ,Apolipoprotein B-100 ,Austria ,Biomarkers ,Cholesterol ,DNA Mutational Analysis ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Heredity ,Humans ,Hyperlipoproteinemia Type II ,Lipoprotein(a) ,Male ,Middle Aged ,Mutation ,Pedigree ,Phenotype ,Polymorphism ,Single Nucleotide ,Receptors ,LDL ,Risk Factors ,Exome Sequencing ,Familial hypercholesterolemia ,LDL cholesterol ,Genetic risk score ,Lipoprotein ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Background and aimsHypercholesterolemia confers susceptibility to cardiovascular disease (CVD). Both serum total cholesterol (TC) and LDL-cholesterol (LDL-C) exhibit a strong genetic component (heritability estimates 0.41-0.50). However, a large part of this heritability cannot be explained by the variants identified in recent extensive genome-wide association studies (GWAS) on lipids. Our aim was to find genetic causes leading to high LDL-C levels and ultimately CVD in a large Austrian family presenting with what appears to be autosomal dominant inheritance for familial hypercholesterolemia (FH).MethodsWe utilized linkage analysis followed by whole-exome sequencing and genetic risk score analysis using an Austrian multi-generational family with various dyslipidemias, including elevated TC and LDL-C, and one family branch with elevated lipoprotein (a) (Lp(a)).ResultsWe did not find evidence for genome-wide significant linkage for LDL-C or apparent causative variants in the known FH genes rather, we discovered a particular family-specific combination of nine GWAS LDL-C SNPs (p = 0.02 by permutation), and putative less severe familial hypercholesterolemia mutations in the LDLR and APOB genes in a subset of the affected family members. Separately, high Lp(a) levels observed in one branch of the family were explained primarily by the LPA locus, including short (
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- 2017
5. Impact of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab on the postprandial responses of triglyceride-rich lipoproteins in type II diabetic subjects
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Taskinen, Marja-Riitta, Björnson, Elias, Andersson, Linda, Kahri, Juhani, Porthan, Kimmo, Matikainen, Niina, Söderlund, Sanni, Pietiläinen, Kirsi, Hakkarainen, Antti, Lundbom, Nina, Nilsson, Ralf, Ståhlman, Marcus, Adiels, Martin, Parini, Paolo, Packard, Chris, and Borén, Jan
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- 2020
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6. The Contribution of GWAS Loci in Familial Dyslipidemias.
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Ripatti, Pietari, Rämö, Joel T, Söderlund, Sanni, Surakka, Ida, Matikainen, Niina, Pirinen, Matti, Pajukanta, Päivi, Sarin, Antti-Pekka, Service, Susan K, Laurila, Pirkka-Pekka, Ehnholm, Christian, Salomaa, Veikko, Wilson, Richard K, Palotie, Aarno, Freimer, Nelson B, Taskinen, Marja-Riitta, and Ripatti, Samuli
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Humans ,Hyperlipidemia ,Familial Combined ,Triglycerides ,Lipoproteins ,LDL ,Apolipoproteins B ,Adult ,Middle Aged ,Female ,Male ,Dyslipidemias ,Cholesterol ,HDL ,Coronary Artery Disease ,Genome-Wide Association Study ,Cholesterol ,HDL ,Hyperlipidemia ,Familial Combined ,Lipoproteins ,LDL ,Genetics ,Developmental Biology - Abstract
Familial combined hyperlipidemia (FCH) is a complex and common familial dyslipidemia characterized by elevated total cholesterol and/or triglyceride levels with over five-fold risk of coronary heart disease. The genetic architecture and contribution of rare Mendelian and common variants to FCH susceptibility is unknown. In 53 Finnish FCH families, we genotyped and imputed nine million variants in 715 family members with DNA available. We studied the enrichment of variants previously implicated with monogenic dyslipidemias and/or lipid levels in the general population by comparing allele frequencies between the FCH families and population samples. We also constructed weighted polygenic scores using 212 lipid-associated SNPs and estimated the relative contributions of Mendelian variants and polygenic scores to the risk of FCH in the families. We identified, across the whole allele frequency spectrum, an enrichment of variants known to elevate, and a deficiency of variants known to lower LDL-C and/or TG levels among both probands and affected FCH individuals. The score based on TG associated SNPs was particularly high among affected individuals compared to non-affected family members. Out of 234 affected FCH individuals across the families, seven (3%) carried Mendelian variants and 83 (35%) showed high accumulation of either known LDL-C or TG elevating variants by having either polygenic score over the 90th percentile in the population. The positive predictive value of high score was much higher for affected FCH individuals than for similar sporadic cases in the population. FCH is highly polygenic, supporting the hypothesis that variants across the whole allele frequency spectrum contribute to this complex familial trait. Polygenic SNP panels improve identification of individuals affected with FCH, but their clinical utility remains to be defined.
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- 2016
7. Clinical significance of CYP11B2 immunostaining in unilateral primary aldosteronism
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Viukari, Marianna, primary, Leijon, Helena, additional, Vesterinen, Tiina, additional, Söderlund, Sanni, additional, Hämäläinen, Päivi, additional, Yliaska, Iina, additional, Rautiainen, Päivi, additional, Rintamäki, Reeta, additional, Soinio, Minna, additional, Pörsti, Ilkka, additional, Nevalainen, Pasi I., additional, and Matikainen, Niina, additional
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- 2023
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8. Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes
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Taskinen, Marja-Riitta, Björnson, Elias, Kahri, Juhani, Söderlund, Sanni, Matikainen, Niina, Porthan, Kimmo, Ainola, Mari, Hakkarainen, Antti, Lundbom, Nina, Fermanelli, Valentina, Fuchs, Johannes, Thorsell, Annika, Kronenberg, Florian, Andersson, Linda, Adiels, Martin, Packard, Chris J., and Borén, Jan
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- 2020
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9. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
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Mardinoglu, Adil, Wu, Hao, Bjornson, Elias, Zhang, Cheng, Hakkarainen, Antti, Räsänen, Sari M., Lee, Sunjae, Mancina, Rosellina M., Bergentall, Mattias, Pietiläinen, Kirsi H., Söderlund, Sanni, Matikainen, Niina, Ståhlman, Marcus, Bergh, Per-Olof, Adiels, Martin, Piening, Brian D., Granér, Marit, Lundbom, Nina, Williams, Kevin J., Romeo, Stefano, Nielsen, Jens, Snyder, Michael, Uhlén, Mathias, Bergström, Göran, Perkins, Rosie, Marschall, Hanns-Ulrich, Bäckhed, Fredrik, Taskinen, Marja-Riitta, and Borén, Jan
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- 2018
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10. Contributors
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Álvarez Pérez, V., primary, Andrea, Lenzi, additional, Andreou, Eleni, additional, Ardern, Chris I., additional, Azushima, Kengo, additional, Baioumi, Alaa Youssef Ahmed Ahmed, additional, Baldari, Carlo, additional, Bell, Samantha, additional, Branco, Renato Chaves Souto, additional, Buendia, Richard, additional, Buendia Jaime, Andres Ricardo, additional, Carneiro, Everardo Magalhães, additional, Carvalho, Heráclito Barbosa, additional, Chen, Phoebe B., additional, Chiara, Marocco, additional, Chourdakis, Michael, additional, da Silva Lima, Natália, additional, De la Cruz Vigo, J.L., additional, de Matos-Neto, Emidio Marques, additional, De Moraes, Augusto César Ferreira, additional, Díaz-Güemes Martín-Portugués, I., additional, Edoardo, Mocini, additional, Greco, Emanuela A., additional, Emerenziani, Gian Pietro, additional, Fatyga, Edyta, additional, Fernandes, Renata C., additional, Figueiredo, Mariana Sarto, additional, Finch, Laura E., additional, Grammatikopoulou, Maria G., additional, Guidetti, Laura, additional, Gutierrez-Blanco, David, additional, Heianza, Yoriko, additional, Hernández Hurtado, L., additional, Ho, Suleen, additional, Hosokawa, Masashi, additional, Ilacqua, Alessandro, additional, Jane, Monica, additional, Janet Tomiyama, A., additional, Janssen-Aguilar, Reinhard, additional, Kanagasabai, Thirumagal, additional, Kang, Inhae, additional, Kerguelen, Alfonso, additional, Kichler, Kandace, additional, Kim, Yoona, additional, Kobayashi, Ryu, additional, Kokot, Teresa, additional, Krakauer, Nir Y., additional, Krakauer, Jesse C., additional, Laviada-Molina, Hugo, additional, Lee, Yunkyoung, additional, Lee, Myoungsook, additional, Llavero, Carolina, additional, Magriplis, Emmanuella, additional, Malczyk, Ewa, additional, Matikainen, Niina, additional, Matos-Azevedo, A.M., additional, McKay, Jenny, additional, Menzo, Emanuele Lo, additional, Micheletti, Thayana O., additional, Miyashita, Kazuo, additional, Molina-Segui, Fernanda, additional, Moreno, Luis A., additional, Muc-Wierzgoń, Małgorzata, additional, Nascimento-Ferreira, Marcus Vinicius, additional, Nawarycz, T., additional, Nehlig, Astrid, additional, Nuffer, Wesley, additional, Nuffer, Monika, additional, Ohki, Kohji, additional, Ostrowska-Nawarycz, L., additional, Pal, Sebely, additional, Park, Yeonhwa, additional, Pimentel, Gustavo D., additional, Pytel, K., additional, Qi, Lu, additional, Ramirez, Raquel, additional, Rendo-Urteaga, Tara, additional, Rosenthal, Raul J., additional, Ruiz-Tovar, Jaime, additional, Sánchez-Margallo, F.M., additional, Serrot, Federico, additional, Silvia, Migliaccio, additional, Söderlund, Sanni, additional, Suzuki, Toru, additional, Szomstein, Samuel, additional, Tamura, Kouichi, additional, Theodoridis, Xenophon, additional, Tiongco-Hofschneider, Lauren, additional, Torres-Leal, Francisco Leonardo, additional, Umuerri, Ejiroghene Martha, additional, Uneda, Kazushi, additional, Vettorazzi, Jean Francisco, additional, Vieira, Eduardo Emanuel Sátiro, additional, Wakui, Hiromichi, additional, Wilemska-Kucharzewska, Katarzyna, additional, Zambrano, Monica, additional, and Zampelas, Antonis, additional
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- 2019
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11. Fibroblast Growth Factor 21 as a Regulator of Energy Metabolism in the Liver and Adipose Tissue
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Matikainen, Niina, primary and Söderlund, Sanni, additional
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- 2019
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12. Cushing's syndrome, pheochromocytoma, or both?
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Kullamaa, Liisa, primary, Ryhänen, Eeva, additional, Söderlund, Sanni, additional, Bärlund, Milla Rosengård, additional, Viukari, Marianna, additional, Muona, Kirsi, additional, Pekkarinen, Tuula, additional, Matikainen, Niina, additional, and Jäntti, Camilla Schalin, additional
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- 2023
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13. Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations
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Taskinen, Marja-Riitta, primary, Björnson, Elias, additional, Matikainen, Niina, additional, Söderlund, Sanni, additional, Rämö, Joel, additional, Ainola, Mari-Mia, additional, Hakkarainen, Antti, additional, Sihlbom, Carina, additional, Thorsell, Annika, additional, Andersson, Linda, additional, Bergh, Per-Olof, additional, Henricsson, Marcus, additional, Romeo, Stefano, additional, Adiels, Martin, additional, Ripatti, Samuli, additional, Laakso, Markku, additional, Packard, Chris J., additional, and Borén, Jan, additional
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- 2022
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14. Role of endogenous incretins in the regulation of postprandial lipoprotein metabolism
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Taskinen, Marja-Riitta, primary, Matikainen, Niina, additional, Björnson, Elias, additional, Söderlund, Sanni, additional, Ainola, Mari, additional, Hakkarainen, Antti, additional, Lundbom, Nina, additional, Sihlbom, Carina, additional, Thorsell, Annika, additional, Andersson, Linda, additional, Adiels, Martin, additional, Hartmann, Bolette, additional, Deacon, Carolyn F, additional, Holst, Jens J, additional, Packard, Chris J, additional, and Borén, Jan, additional
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- 2022
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15. Role of endogenous incretins in the regulation of postprandial lipoprotein metabolism
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Taskinen, Marja-Riitta, Matikainen, Niina, Björnson, Elias, Söderlund, Sanni, Ainola, Mari, Hakkarainen, Antti, Lundbom, Nina, Sihlbom, Carina, Thorsell, Annika, Andersson, Linda, Adiels, Martin, Hartmann, Bolette, Deacon, Carolyn F., Holst, Jens J, Packard, Chris J, Borén, Jan, Taskinen, Marja-Riitta, Matikainen, Niina, Björnson, Elias, Söderlund, Sanni, Ainola, Mari, Hakkarainen, Antti, Lundbom, Nina, Sihlbom, Carina, Thorsell, Annika, Andersson, Linda, Adiels, Martin, Hartmann, Bolette, Deacon, Carolyn F., Holst, Jens J, Packard, Chris J, and Borén, Jan
- Abstract
Objective: Incretins are known to influence lipid metabolism in the intestine when administered as pharmacologic agents. The aggregate influence of endogenous incretins on chylomicron production and clearance is less clear, particularly in light of opposing effects of co-secreted hormones. Here, we tested the hypothesis that physiological levels of incretins may impact on production or clearances rates of chylomicrons and VLDL.Design and methods: A group of 22 overweight/obese men was studied to determine associations between plasma levels of glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) after a fat-rich meal and the production and clearance rates of apoB48- and apoB100-containing triglyceride-rich lipoproteins. Subjects were stratified by above- and below-median incretin response (area under the curve).Results: Stratification yielded subgroups that differed about two-fold in incretin response. There were neither differences in apoB48 production rates in chylomicrons or VLDL fractions nor in apoB100 or triglyceride kinetics in VLDL between men with above- vs below-median incretin responses. The men with above-median GLP-1 and GLP-2 responses exhibited higher postprandial plasma and chylomicron triglyceride levels, but this could not be related to altered kinetic parameters. No differences were found between incretin response subgroups and particle clearance rates.Conclusion: We found no evidence for a regulatory effect of endogenous incretins on contemporaneous chylomicron or VLDL metabolism following a standardised fat-rich meal. The actions of incretins at pharmacological doses may not be reflected at physiological levels of these hormones.
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- 2022
16. ApoA-II HDL Catabolism and Its Relationships With the Kinetics of ApoA-I HDL and of VLDL1, in Abdominal Obesity
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Vergès, Bruno, Adiels, Martin, Boren, Jan, Barrett, Peter Hugh, Watts, Gerald F., Chan, Dick, Duvillard, Laurence, Söderlund, Sanni, Matikainen, Niina, Kahri, Juhani, Lundbom, Nina, Lundbom, Jesper, Hakkarainen, Antti, Aho, Serge, Simoneau-Robin, Isabelle, and Taskinen, Marja-Riitta
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- 2016
17. Increased apolipoprotein E level and reduced high-density lipoprotein mean particle size associate with low high-density lipoprotein cholesterol and features of metabolic syndrome
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Söderlund, Sanni, Watanabe, Hiroshi, Ehnholm, Christian, Jauhiainen, Matti, and Taskinen, Marja-Riitta
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- 2010
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18. Effects of liraglutide on the metabolism of triglyceride‐rich lipoproteins in type 2 diabetes
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Taskinen, Marja‐Riitta, Björnson, Elias, Matikainen, Niina, Söderlund, Sanni, Pietiläinen, Kirsi H., Ainola, Mari, Hakkarainen, Antti, Lundbom, Nina, Fuchs, Johannes, Thorsell, Annika, Andersson, Linda, Adiels, Martin, Packard, Chris J., and Borén, Jan
- Abstract
Aim: \ud To elucidate the impact of liraglutide on the kinetics of apolipoprotein (apo)B48- and apoB100-containing triglyceride-rich lipoproteins in subjects with type 2 diabetes (T2D) after a single fat-rich meal.\ud \ud Materials and Methods: \ud Subjects with T2D were included in a study to investigate postprandial apoB48 and apoB100 metabolism before and after 16 weeks on l.8 mg/day liraglutide (n = 14) or placebo (n = 4). Stable isotope tracer and compartmental modelling techniques were used to determine the impact of liraglutide on chylomicron and very low-density lipoprotein (VLDL) production and clearance after a single fat-rich meal.\ud \ud Results: \ud Liraglutide reduced apoB48 synthesis in chylomicrons by 60% (p
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- 2021
19. Effects of PNPLA3 I148M on hepatic lipid and very‐low‐density lipoprotein metabolism in humans
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Borén, Jan, primary, Adiels, Martin, additional, Björnson, Elias, additional, Matikainen, Niina, additional, Söderlund, Sanni, additional, Rämö, Joel, additional, Henricsson, Marcus, additional, Ripatti, Pietari, additional, Ripatti, Samuli, additional, Palotie, Aarno, additional, Mancina, Rosellina M., additional, Ainola, Mari, additional, Hakkarainen, Antti, additional, Romeo, Stefano, additional, Packard, Chris J., additional, and Taskinen, Marja‐Riitta, additional
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- 2021
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20. Paradoxical Dissociation Between Hepatic Fat Content and De Novo Lipogenesis Due to PNPLA3 Sequence Variant
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Mancina, Rosellina M., Matikainen, Niina, Maglio, Cristina, Söderlund, Sanni, Lundbom, Nina, Hakkarainen, Antti, Rametta, Raffaela, Mozzi, Enrico, Fargion, Silvia, Valenti, Luca, Romeo, Stefano, Taskinen, Marja-Riitta, and Borén, Jan
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- 2015
21. Interrelationships Between the Kinetics of VLDL Subspecies and HDL Catabolism in Abdominal Obesity: A Multicenter Tracer Kinetic Study
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Vergès, Bruno, Adiels, Martin, Boren, Jan, Barrett, Peter Hugh, Watts, Gerald F., Chan, Dick, Duvillard, Laurence, Söderlund, Sanni, Matikainen, Niina, Kahri, Juhani, Robin, Isabelle, and Taskinen, Marja-Riitta
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- 2014
22. Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes
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Taskinen, Marja-Riitta, primary, Björnson, Elias, additional, Kahri, Juhani, additional, Söderlund, Sanni, additional, Matikainen, Niina, additional, Porthan, Kimmo, additional, Ainola, Mari, additional, Hakkarainen, Antti, additional, Lundbom, Nina, additional, Fermanelli, Valentina, additional, Fuchs, Johannes, additional, Thorsell, Annika, additional, Kronenberg, Florian, additional, Andersson, Linda, additional, Adiels, Martin, additional, Packard, Chris J., additional, and Borén, Jan, additional
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- 2021
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23. Effects of TM6SF2 E167K on hepatic lipid and very low-density lipoprotein metabolism in humans
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Borén, Jan, primary, Adiels, Martin, additional, Björnson, Elias, additional, Matikainen, Niina, additional, Söderlund, Sanni, additional, Rämö, Joel, additional, Ståhlman, Marcus, additional, Ripatti, Pietari, additional, Ripatti, Samuli, additional, Palotie, Aarno, additional, Mancina, Rosellina M., additional, Hakkarainen, Antti, additional, Romeo, Stefano, additional, Packard, Chris J., additional, and Taskinen, Marja-Riitta, additional
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- 2020
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24. Effects of PNPLA3 I148M on hepatic lipid and very‐low‐density lipoprotein metabolism in humans.
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Borén, Jan, Adiels, Martin, Björnson, Elias, Matikainen, Niina, Söderlund, Sanni, Rämö, Joel, Henricsson, Marcus, Ripatti, Pietari, Ripatti, Samuli, Palotie, Aarno, Mancina, Rosellina M., Ainola, Mari, Hakkarainen, Antti, Romeo, Stefano, Packard, Chris J., and Taskinen, Marja‐Riitta
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LIPIDS ,LIPOPROTEINS ,METABOLISM ,LIPID metabolism ,TRIGLYCERIDES - Abstract
Background: The phospholipase domain‐containing 3 gene (PNPLA3)‐148M variant is associated with liver steatosis but its influence on the metabolism of triglyceride‐rich lipoproteins remains unclear. Here, we investigated the kinetics of large, triglyceride‐rich very‐low‐density lipoprotein (VLDL), (VLDL1), and smaller VLDL2 in homozygotes for the PNPLA3‐148M variant. Methods and results: The kinetics of apolipoprotein (apo) B100 (apoB100) and triglyceride in VLDL subfractions were analysed in nine subjects homozygous for PNPLA3‐148M and nine subjects homozygous for PNPLA3‐148I (controls). Liver fat was >3‐fold higher in the 148M subjects. Production rates for apoB100 and triglyceride in VLDL1 did not differ significantly between the two groups. Likewise, production rates for VLDL2‐apoB100 and ‐triglyceride, and fractional clearance rates for both apoB100 and triglyceride in VLDL1 and VLDL2, were not significantly different. Conclusions: Despite the higher liver fat content in PNPLA3 148M homozygotes, there was no increase in VLDL production. Equally, VLDL production was maintained at normal levels despite the putative impairment in cytosolic lipid hydrolysis in these subjects. [ABSTRACT FROM AUTHOR]
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- 2022
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25. Role of apolipoprotein C-III overproduction in diabetic dyslipidemia
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Adiels, Martin, Taskinen, Marja-Riitta, Björnson, Elias, Andersson, Linda, Matikainen, Niina, Söderlund, Sanni, Kahri, Juhani, Hakkarainen, Antti, Lundbom, Nina, Sihlbom, Carina, Thorsell, Annika, Zhou, Haihong, Pietiläinen, Kirsi H., Packard, Chris, and Borén, Jan
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lipids (amino acids, peptides, and proteins) - Abstract
Aims:\ud \ud To investigate how apolipoprotein C‐III (apoC‐III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC‐III, and whether improvement of glycaemic control using the glucagon‐like peptide‐1 analogue liraglutide for 16 weeks modifies apoC‐III dynamics.\ud Materials and Methods:\ud \ud Postprandial apoC‐III kinetics were assessed after a bolus injection of [5,5,5‐2H3]leucine using ultrasensitive mass spectrometry techniques. We compared apoC‐III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non‐diabetic subjects. Liver fat content, subcutaneous abdominal and intra‐abdominal fat were determined using proton magnetic resonance spectroscopy.\ud Results:\ud \ud Improved glycaemic control by liraglutide therapy for 16 weeks significantly reduced apoC‐III secretion rate (561 ± 198 vs. 652 ± 196 mg/d, P = 0.03) and apoC‐III levels (10.0 ± 3.8 vs. 11.7 ± 4.3 mg/dL, P = 0.035) in subjects with type 2 diabetes. Change in apoC‐III secretion rate was significantly associated with the improvement in indices of glucose control (r = 0.67; P = 0.009) and change in triglyceride area under the curve (r = 0.59; P = 0.025). In line with this, the apoC‐III secretion rate was higher in subjects with type 2 diabetes compared with BMI‐matched non‐diabetic subjects (676 ± 208 vs. 505 ± 174 mg/d, P = 0.042).\ud Conclusions:\ud \ud The results reveal that the secretion rate of apoC‐III is associated with elevation of triglyceride‐rich lipoproteins in subjects with type 2 diabetes, potentially through the influence of glucose homeostasis on the production of apoC‐III.
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- 2019
26. Liraglutide treatment improves postprandial lipid metabolism and cardiometabolic risk factors in humans with adequately controlled type 2 diabetes : A single-centre randomized controlled study
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Matikainen, Niina, Söderlund, Sanni, Björnson, Elias, Pietiläinen, Kirsi, Hakkarainen, Antti, Lundbom, Nina, Taskinen, Marja-Riitta, Boren, Jan, Clinicum, Diabetes and Obesity Research Program, Research Programs Unit, Department of Medicine, Endokrinologian yksikkö, University of Helsinki, HUS Abdominal Center, Faculty of Medicine, HUS Internal Medicine and Rehabilitation, Department of Diagnostics and Therapeutics, HUS Medical Imaging Center, Marja-Riitta Taskinen Research Group, and HUS Heart and Lung Center
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liraglutide ,remnant lipoproteins ,EXENATIDE ,PLACEBO ,METFORMIN ,atherogenic dyslipidaemia ,liver fat ,REMNANT CHOLESTEROL ,RECEPTOR AGONISTS ,GLP-1-agonist ,LIPOPROTEINS ,de novo lipogenesis ,apolipoprotein C3 ,3121 General medicine, internal medicine and other clinical medicine ,PARTICLES ,VILDAGLIPTIN THERAPY ,TRIGLYCERIDE ,postprandial lipids ,FATTY LIVER-DISEASE - Abstract
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.
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- 2019
27. Onko HDL hyvä vai paha verisuonille?
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Söderlund, Sanni, Taskinen, Marja-Riitta, Tutkimusohjelmayksikkö, Diabetes ja lihavuus -tutkimusohjelma, Clinicum, Sisätautien osasto, Helsingin yliopisto, Tutkimusryhmä Marja-Riitta Taskinen, HUS Sisätaudit ja kuntoutus, and HUS Sydän- ja keuhkokeskus
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3121 Yleislääketiede, sisätaudit ja muut kliiniset lääketieteet ,GeneralLiterature_INTRODUCTORYANDSURVEY ,Cardiovascular Diseases ,Cholesterol, HDL ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Atherosclerosis ,Lipoproteins, HDL ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Abstract
English summary
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- 2018
28. Polygenic Hyperlipidemias and Coronary Artery Disease Risk
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Ripatti, Pietari, primary, Rämö, Joel T, additional, Mars, Nina J, additional, Söderlund, Sanni, additional, Benner, Christian, additional, Surakka, Ida, additional, Kiiskinen, Tuomo, additional, Havulinna, Aki S, additional, Palta, Priit, additional, Freimer, Nelson B, additional, Salomaa, Veikko, additional, Pirinen, Matti, additional, Palotie, FinnGen Aarno, additional, Taskinen, Marja-Riitta, additional, and Ripatti, Samuli, additional
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- 2019
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29. CORONARY ARTERY DISEASE RISK AND LIPIDOMIC PROFILES IN FAMILIAL HYPERLIPIDEMIAS
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Rämö, Joel, primary, Ripatti, Pietari, additional, Tabassum, Rubina, additional, Söderlund, Sanni, additional, Matikainen, Niina, additional, Gerl, Mathias J., additional, Klose, Christian, additional, Surma, Michal, additional, Stitziel, Nathan O., additional, Havulinna, Aki S., additional, Salomaa, Veikko, additional, Freimer, Nelson B., additional, Jauhiainen, Matti, additional, Palotie, Aarno, additional, Taskinen, Marja-Riitta, additional, Simons, Kai, additional, and Ripatti, Samuli, additional
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- 2019
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30. Effect of HDL composition and particle size on the resistance of HDL to the oxidation
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Jauhiainen Matti, Söderlund Sanni, Shuhei Nakanishi, and Taskinen Marja-Riitta
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Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Objectives To study the resistance of HDL particles to direct oxidation in respect to the distribution of HDL particles. Design and Methods We studied HDL composition, subclass distribution, and the kinetics of CuSO4-induced oxidation of total HDL and HDL3 in vitro in 36 low-HDL-C subjects and in 41 control subjects with normal HDL-C. Results The resistance of HDL3 to oxidation, as assessed from the propagation rate was significantly higher than that of total HDL. The propagation rate and diene formation during HDL oxidation in vitro was attenuated in HDL derived from low-HDL-C subjects. Propagation rate and maximal diene formation during total HDL oxidation correlated significantly with HDL mean particle size. The propagation rate of total HDL oxidation in vitro displayed a significant positive association with HDL2 particle mass and HDL mean particle size by multiple regression analyses. Conclusions These observations highlight that the distribution of HDL subpopulations has important implications for the potential of HDL as an anti-oxidant source.
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- 2010
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31. Personal model-assisted identification of NAD(+) and glutathione metabolism as intervention target in NAFLD
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Mardinoglu , Adil, Bjornson , Elias, Zhang , Cheng, Klevstig , Martin, Söderlund , Sanni, Ståhlman , Marcus, Adiels , Martin, Hakkarainen , Antti, Lundbom , Nina, Kilicarslan , Murat, Hallström , Björn M, Lundbom , Jesper, Verges , Bruno, Barrett , Peter Hugh R, Watts , Gerald F, Serlie , Mireille J, Nielsen , Jens, Uhlén , Mathias, Smith , Ulf, Marschall , Hanns-Ulrich, Taskinen , Marja-Riitta, Boren , Jan, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Science for Life Laboratory [Solna], Royal Institute of Technology [Stockholm] ( KTH ), Department of Biology and Biological Engineering, Chalmers University of Technology [Göteborg], Sahlgrenska University Hospital, Department of molecular and clinical medicine [Gothenburg], University of Gothenburg ( GU ), University of Helsinki [Helsinki], Helsinki University Hospital, HUS Medical Imaging Center (Helsinky), University of Helsinki [Helsinki]-Helsinki University Central Hospital, Department of Endocrinology and Metabolism (Academic Medical Center, Amsterdam), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Equipe PADYS (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Flow Interactive, Technical University of Denmark, National Institute of Aquatic Resources, Science for Life Laboratory, Royal Institute of Technology in Stockholm ( KTH ), School of Earth Sciences [Bristol], University of Bristol [Bristol], Woods Hole Oceanographic Institution ( WHOI ), Royal Institute of Technology [Stockholm] (KTH ), Sahlgrenska University Hospital [Gothenburg], University of Gothenburg (GU), University of Helsinki, HUS Medical Imaging Center [Helsinki] (HUS-MIC), HiLIFE - Neuroscience Center (NC), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki-Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Institute of Technology in Stockholm (KTH), Woods Hole Oceanographic Institution (WHOI), HUS Internal Medicine and Rehabilitation, Research Programs Unit, Diabetes and Obesity Research Program, Clinicum, Department of Diagnostics and Therapeutics, HUS Medical Imaging Center, Marja-Riitta Taskinen Research Group, Helsinki University Hospital Area, and HUS Heart and Lung Center
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AMINO-ACID-METABOLISM ,GENOME-SCALE ,INSULIN-RESISTANCE ,TISSUE BLOOD-FLOW ,personalized genome‐scale metabolic modeling ,DRUG TARGETS ,MUSCLE ,serine ,ADIPOSE-TISSUE ,HEPATOCELLULAR-CARCINOMA ,OBESITY ,NAFLD ,personalized genome-scale metabolic modeling ,1182 Biochemistry, cell and molecular biology ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,3111 Biomedicine ,glutathione ,[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,FATTY LIVER-DISEASE - Abstract
IF 10.5; International audience; To elucidate the molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome-scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD(+) and glutathione (GSH) in subjects with high HS Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepatic expression levels of the associated enzymes further pointed to altered de novo GSH synthesis. To assess the effect of GSH and NAD(+) repletion on the development of NAFLD, we added precursors for GSH and NAD(+) biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof-of-concept human study, we found improved liver function and decreased HS after supplementation with serine (a precursor to glycine) and hereby propose a strategy for NAFLD treatment.
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- 2017
32. Genetics of human plasma lipidome: Understanding lipid metabolism and its link to diseases beyond traditional lipids
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Tabassum, Rubina, primary, Rämö, Joel T., additional, Ripatti, Pietari, additional, Koskela, Jukka T., additional, Kurki, Mitja, additional, Karjalainen, Juha, additional, Hassan, Shabbeer, additional, Nunez-Fontarnau, Javier, additional, Kiiskinen, Tuomo T.J., additional, Söderlund, Sanni, additional, Matikainen, Niina, additional, Gerl, Mathias J., additional, Surma, Michal A., additional, Klose, Christian, additional, Stitziel, Nathan O., additional, Laivuori, Hannele, additional, Havulinna, Aki S., additional, Service, Susan K., additional, Salomaa, Veikko, additional, Pirinen, Matti, additional, Jauhiainen, Matti, additional, Daly, Mark J., additional, Freimer, Nelson B., additional, Palotie, Aarno, additional, Taskinen, Marja-Riitta, additional, Simons, Kai, additional, and Ripatti, Samuli, additional
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- 2018
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33. Liraglutide treatment improves postprandial lipid metabolism and cardiometabolic risk factors in humans with adequately controlled type 2 diabetes: A single‐centre randomized controlled study
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Matikainen, Niina, primary, Söderlund, Sanni, additional, Björnson, Elias, additional, Pietiläinen, Kirsi, additional, Hakkarainen, Antti, additional, Lundbom, Nina, additional, Taskinen, Marja‐Riitta, additional, and Borén, Jan, additional
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- 2018
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34. Coronary artery disease risk and lipidomic profiles are similar in familial and population-ascertained hyperlipidemias
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Rämö, Joel T., primary, Ripatti, Pietari, additional, Tabassum, Rubina, additional, Söderlund, Sanni, additional, Matikainen, Niina, additional, Gerl, Mathias J., additional, Klose, Christian, additional, Stitziel, athan O., additional, Havulinna, Aki S., additional, Salomaa, Veikko, additional, Freimer, Nelson B., additional, Jauhiainen, Matti, additional, Palotie, Aarno, additional, Taskinen, Marja-Riitta, additional, Simons, Kai, additional, and Ripatti, Samuli, additional
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- 2018
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35. Low-dose valganciclovir prohylaxis is efficacious and safe in cytomegalovirus seropositive heart transplant recipients with anti-thymocyte globulin
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Eriksson, Mari, primary, Jokinen, Janne J., additional, Söderlund, Sanni, additional, Hämmäinen, Pekka, additional, Lommi, Jyri, additional, and Lemström, Karl, additional
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- 2018
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36. Family-specific aggregation of lipid GWAS variants confers the susceptibility to familial hypercholesterolemia in a large Austrian family
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Nikkola, Elina, primary, Ko, Arthur, additional, Alvarez, Marcus, additional, Cantor, Rita M., additional, Garske, Kristina, additional, Kim, Elliot, additional, Gee, Stephanie, additional, Rodriguez, Alejandra, additional, Muxel, Reinhard, additional, Matikainen, Niina, additional, Söderlund, Sanni, additional, Motazacker, Mahdi M., additional, Borén, Jan, additional, Lamina, Claudia, additional, Kronenberg, Florian, additional, Schneider, Wolfgang J., additional, Palotie, Aarno, additional, Laakso, Markku, additional, Taskinen, Marja-Riitta, additional, and Pajukanta, Päivi, additional
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- 2017
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37. Mass spectrometry of circulating lipid species highlights similarity of familial hyperlipidemias and hyperlipidemias in the general population
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Rämö, Joel, primary, Ripatti, Pietari, additional, Tabassum, Rubina, additional, Söderlund, Sanni, additional, Matikainen, Niina, additional, Gerl, Mathias, additional, Klose, Christian, additional, Stitziel, Nathan, additional, Havulinna, Aki, additional, Salomaa, Veikko, additional, Freimer, Nelson, additional, Palotie, Aarno, additional, Simons, K.A.I., additional, Taskinen, Marja -Riitta, additional, and Ripatti, Samuli, additional
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- 2017
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38. Polygenic hyperlipidemia and coronary artery disease risk
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Ripatti, Pietari, primary, Rämö, Joel, additional, Söderlund, Sanni, additional, Surakka, Ida, additional, Matikainen, Niina, additional, Salomaa, Veikko, additional, Freimer, Nelson, additional, Palotie, Aarno, additional, Taskinen, Marja –Riitta, additional, and Ripatti, Samuli, additional
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- 2017
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39. Personal model‐assisted identification of NAD + and glutathione metabolism as intervention target in NAFLD
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Mardinoglu, Adil, primary, Bjornson, Elias, additional, Zhang, Cheng, additional, Klevstig, Martina, additional, Söderlund, Sanni, additional, Ståhlman, Marcus, additional, Adiels, Martin, additional, Hakkarainen, Antti, additional, Lundbom, Nina, additional, Kilicarslan, Murat, additional, Hallström, Björn M, additional, Lundbom, Jesper, additional, Vergès, Bruno, additional, Barrett, Peter Hugh R, additional, Watts, Gerald F, additional, Serlie, Mireille J, additional, Nielsen, Jens, additional, Uhlén, Mathias, additional, Smith, Ulf, additional, Marschall, Hanns‐Ulrich, additional, Taskinen, Marja‐Riitta, additional, and Boren, Jan, additional
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- 2017
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40. Minor Contribution of Endogenous GLP-1 and GLP-2 to Postprandial Lipemia in Obese Men
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Matikainen, Niina, Björnson, Elias, Söderlund, Sanni, Borén, Christofer, Eliasson, Björn, Pietiläinen, Kirsi H, Bogl, Leonie H, Hakkarainen, Antti, Lundbom, Nina, Rivellese, Angela, Riccardi, Gabriele, Després, Jean-Pierre, Alméras, Natalie, Holst, Jens Juul, Deacon, Carolyn F, Borén, Jan, Taskinen, Marja-Riitta, Matikainen, Niina, Björnson, Elias, Söderlund, Sanni, Borén, Christofer, Eliasson, Björn, Pietiläinen, Kirsi H, Bogl, Leonie H, Hakkarainen, Antti, Lundbom, Nina, Rivellese, Angela, Riccardi, Gabriele, Després, Jean-Pierre, Alméras, Natalie, Holst, Jens Juul, Deacon, Carolyn F, Borén, Jan, and Taskinen, Marja-Riitta
- Abstract
CONTEXT: Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified.OBJECTIVE: To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal.DESIGN: Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5-40.2 kg/m2) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal.MAIN OUTCOME MEASURES: Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins.RESULTS: The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively). Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest.CONCLUSIONS: In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor.
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- 2016
41. Minor Contribution of Endogenous GLP-1 and GLP-2 to Postprandial Lipemia in Obese Men
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Matikainen, Niina, primary, Björnson, Elias, additional, Söderlund, Sanni, additional, Borén, Christofer, additional, Eliasson, Björn, additional, Pietiläinen, Kirsi H., additional, Bogl, Leonie H., additional, Hakkarainen, Antti, additional, Lundbom, Nina, additional, Rivellese, Angela, additional, Riccardi, Gabriele, additional, Després, Jean-Pierre, additional, Alméras, Natalie, additional, Holst, Jens Juul, additional, Deacon, Carolyn F., additional, Borén, Jan, additional, and Taskinen, Marja-Riitta, additional
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- 2016
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42. HDL subspecies : association with low HDL-C, obesity, and metabolic syndrome
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Söderlund, Sanni, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Division of Cardiology, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, Savolainen, Markku, and Taskinen, Marja-Riitta
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medicine (science) ,medicin ,nutritional and metabolic diseases ,lipids (amino acids, peptides, and proteins) ,lääketiede - Abstract
AIMS An independent, powerful coronary heart disease (CHD) predictor is a low level of high-density lipoprotein cholesterol (HDL-C). Discoidal preβ-HDL particles and large HDL2 particles are the primary cholesterol acceptors in reverse cholesterol transport, a key anti-atherogenic HDL mechanism. The quality of HDL subspecies may provide better markers of HDL functionality than does HDL-C alone. We aimed I) to study whether alterations in the HDL subspecies profile exist in low-HDL-C subjects II) to explore the relationship of any changes in HDL subspecies profile in relation to atherosclerosis and metabolic syndrome; III) to elucidate the impact of genetics and acquired obesity on HDL subspecies distribution. SUBJECTS The study consisted of 3 cohorts: A) Finnish families with low HDL-C and premature CHD (Study I: 67 subjects with familial low HDL-C and 64 controls; Study II: 83 subjects with familial low HDL-C, 65 family members with normal HDL-C, and 133 controls); B) a cohort of 113 low- and 133 high-HDL-C subjects from the Health 2000 Health Examination Survey carried out in Finland (Study III); and C) a Finnish cohort of healthy young adult twins (52 monozygotic and 89 dizygotic pairs) (Study IV). RESULTS AND CONCLUSIONS The subjects with familial low HDL-C had a lower preβ-HDL concentration than did controls, and the low-HDL-C subjects displayed a dramatic reduction (50-70%) in the proportion of large HDL2b particles. The subjects with familial low HDL-C had increased carotid atherosclerosis measured as intima-media-thickness (IMT), and HDL2b particles correlated negatively with IMT. The reduction in both key cholesterol acceptors, preβ-HDL and HDL2 particles, supports the concept of impaired reverse cholesterol transport contributing to the higher CHD risk in low-HDL-C subjects. The family members with normal HDL-C and the young adult twins with acquired obesity showed a reduction in large HDL2 particles and an increase in small HDL3 particles, which may be the first changes leading to the lowering of HDL-C. The low-HDL-C subjects had a higher serum apolipoprotein E (apoE) concentration, which correlated positively with the metabolic syndrome components (waist circumference, TG, and glucose), highlighting the need for a better understanding of apoE metabolism in human atherosclerosis. In the twin study, the increase in small HDL3b particles was associated with obesity independent of genetic effects. The heritability estimate, of 73% for HDL-C and 46 to 63% for HDL subspecies, however, demonstrated a strong genetic influence. These results suggest that the relationship between obesity and lipoproteins depends on different elements in each subject. Finally, instead of merely elevating HDL-C, large HDL2 particles and discoidal preβ-HDL particles may provide beneficial targets for HDL-targeted therapy. Pieni HDL-kolesterolin määrä on sepelvaltimotaudin vaaratekijä. Monimuotoiset HDL-hiukkaset suojaavat verisuonia mm. kuljettaen ylimääräistä kolesterolia soluista maksaan. HDL-hiukkasten jakauma ja laatu saattavat vaikuttaa siihen, miten hyvin HDL-hiukkaset suojaavat sepelvaltimotaudilta. Tämän tutkimuksen tavoitteet olivat selvittää I) onko henkilöillä, joilla on matala HDL-kolesterolin pitoisuus, muutoksia HDL-hiukkasten jakaumassa, II) liittyvätkö mahdolliset muutokset valtimonkovettumatautiin ja metaboliseen oireyhtymään, III) perimän ja ylipainon vaikutus HDL-hiukkasten jakaumaan. Tutkimus koostui kolmesta kohortista: A) suomalaisista perheistä, joissa esiintyy matalaa HDL-kolesterolin pitoisuutta ja sepelvaltimotautia varhaisella iällä (osatutkimus I: 67 perheenjäsentä, joilla on matala HDL-kolesterolin pitoisuus sekä 64 tervettä verrokkia, osatutkimus II: 83 perheenjäsentä, joilla on matala HDL-kolesterolin pitoisuus, 65 perheenjäsentä, joilla on normaali HDL-kolesterolin pitoisuus, sekä 133 tervettä verrokkia), B) suomalaisesta Terveys 2000 tutkimuksesta (113 henkilöä, joilla on matala HDL-kolesterolin pitoisuus ja 133 henkilöä, joilla on korkea HDL-kolesterolin pitoisuus), C) suomalaisista, nuorista aikuisista kaksosista (52 identtistä ja 89 epäidenttistä paria). Tutkimuksessa todettiin, että henkilöillä, joilla on perinnöllinen matala HDL-kolesterolin pitoisuus, on verrokkeihin nähden pienempi kiekkomaisten preβ-HDL-hiukkasten pitoisuus. Isojen, pyöreiden HDL2b-hiukkasten suhteellinen määrä oli huomattavasti pienentynyt (50-70%) ja pienten HDL3-hiukkasten osuus suurentunut henkilöillä, joilla on matala HDL-kolesterolin pitoisuus. Henkilöillä, joilla on perinnöllinen matala HDL-kolesterolin pitoisuus, kaulavaltimoiden seinämät olivat paksuuntuneet heijastaen heidän sepelvaltimotautiriskiään. HDL2b-hiukkasten osuus oli käänteisesti yhteydessä kaulavaltimoiden seinämäpaksuuteen. HDL2b- ja preβ-HDL-hiukkaset ovat ensisijaisia kolesterolin vastaanottajia soluista maksaan. Tulos niiden vähentymisestä tukee käsitystä siitä, että henkilöillä, joilla on matala HDL-kolesterolin pitoisuus, kolesterolin kuljetus soluista maksaan on heikentynyt johtaen suurentuneeseen sepelvaltimotaudin riskiin. Myös perheenjäsenillä, joilla HDL-kolesterolin pitoisuus oli normaali, HDL2b-hiukkasten osuus oli pienentynyt ja HDL3-hiukkasten osuus suurentunut verrokkeihin nähden. Samanlainen muutos HDL-hiukkasten jakaumassa nähtiin ylipainoisilla, nuorilla aikuisilla kaksosilla normaalipainoisiin kaksosiin nähden. HDL2-hiukkasten osuuden vähenemä saattaakin olla ensimmäinen muutos, joka johtaa HDL-kolesterolin pitoisuuden pienenemiseen. Kaksostutkimuksessa havaittiin, että sekä ylipaino että perinnölliset tekijät vaikuttavat HDL-hiukkasten jakaumaan. Terveys 2000 tutkimuksessa matalan HDL-kolesterolin pitoisuuden henkilöillä seerumin kohonnut apolipoproteiini E:n (apoE) pitoisuus oli yhteydessä metabolisen oireyhtymään (suurentuneeseen vyötärönympäryyteen, triglyseridipitoisuuteen ja verensokeriin). Lisäksi HDL-hiukkasten apoE-jakauma oli heillä muuntunut. Tulos valotti aiemmin niukasti tunnettua apoE:n roolia HDL:n aineenvaihdunnassa. Tutkimuksen tulokset viittaavat siihen, että uusia HDL-kolesteroliin vaikuttavia lääkehoitoja kehitettäessä on tärkeää ottaa huomioon niiden vaikutus HDL-hiukkasten jakaumaan.
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- 2011
43. Kinetic and Related Determinants of Plasma Triglyceride Concentration in Abdominal Obesity
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Borén, Jan, primary, Watts, Gerald F., additional, Adiels, Martin, additional, Söderlund, Sanni, additional, Chan, Dick C., additional, Hakkarainen, Antti, additional, Lundbom, Jesper, additional, Lundbom, Nina, additional, Matikainen, Niina, additional, Kahri, Juhani, additional, Vergès, Bruno, additional, Barrett, P. Hugh R., additional, and Taskinen, Marja-Riitta, additional
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- 2015
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44. Personal model-assisted identification of NAD+ and glutathione metabolism as intervention target in NAFLD.
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Mardinoglu, Adil, Bjornson, Elias, Zhang, Cheng, Klevstig, Martina, Söderlund, Sanni, Ståhlman, Marcus, Adiels, Martin, Hakkarainen, Antti, Lundbom, Nina, Kilicarslan, Murat, Hallström, Björn M, Lundbom, Jesper, Vergès, Bruno, Barrett, Peter Hugh R, Watts, Gerald F, Serlie, Mireille J, Nielsen, Jens, Uhlén, Mathias, Smith, Ulf, and Marschall, Hanns‐Ulrich
- Subjects
GLUTATHIONE ,FATTY liver ,THERAPEUTICS ,LIVER cells ,METABOLOMICS ,GLYCINE ,LIVER function tests - Abstract
To elucidate the molecular mechanisms underlying non-alcoholic fatty liver disease ( NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis ( HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome-scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD
+ and glutathione ( GSH) in subjects with high HS. Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepatic expression levels of the associated enzymes further pointed to altered de novo GSH synthesis. To assess the effect of GSH and NAD+ repletion on the development of NAFLD, we added precursors for GSH and NAD+ biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof-of-concept human study, we found improved liver function and decreased HS after supplementation with serine (a precursor to glycine) and hereby propose a strategy for NAFLD treatment. [ABSTRACT FROM AUTHOR]- Published
- 2017
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45. Hepatic lipogenesis and a marker of hepatic lipid oxidation, predict postprandial responses of triglyceride‐rich lipoproteins
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Matikainen, Niina, primary, Adiels, Martin, additional, Söderlund, Sanni, additional, Stennabb, Sanna, additional, Ahola, Tytti, additional, Hakkarainen, Antti, additional, Borén, Jan, additional, and Taskinen, Marja‐Riitta, additional
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- 2014
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46. Genomic, transcriptomic, and lipidomic profiling highlights the role of inflammation in individuals with low high-density lipoprotein cholesterol
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Laurila, Pirkka-Pekka, Surakka, Ida, Sarin, Antti-Pekka, Yetukuri, Laxman, Hyötyläinen, Tuulia, Söderlund, Sanni, Naukkarinen, Jussi, Tang, Jing, Kettunen, Johannes, Mirel, Daniel B, Soronen, Jarkko, Lehtimäki, Terho, Ruokonen, Aimo, Ehnholm, Christian, Eriksson, Johan G., Salomaa, Veikko, Jula, Antti, Raitakari, Olli T, Järvelin, Marjo-Riitta, Palotie, Aarno, Peltonen, Leena, Oresic, Matej, Jauhiainen, Matti, Taskinen, Marja-Riitta, Ripatti, Samuli, Laurila, Pirkka-Pekka, Surakka, Ida, Sarin, Antti-Pekka, Yetukuri, Laxman, Hyötyläinen, Tuulia, Söderlund, Sanni, Naukkarinen, Jussi, Tang, Jing, Kettunen, Johannes, Mirel, Daniel B, Soronen, Jarkko, Lehtimäki, Terho, Ruokonen, Aimo, Ehnholm, Christian, Eriksson, Johan G., Salomaa, Veikko, Jula, Antti, Raitakari, Olli T, Järvelin, Marjo-Riitta, Palotie, Aarno, Peltonen, Leena, Oresic, Matej, Jauhiainen, Matti, Taskinen, Marja-Riitta, and Ripatti, Samuli
- Abstract
OBJECTIVE: Low high-density lipoprotein cholesterol (HDL-C) is associated with cardiometabolic pathologies. In this study, we investigate the biological pathways and individual genes behind low HDL-C by integrating results from 3 high-throughput data sources: adipose tissue transcriptomics, HDL lipidomics, and dense marker genotypes from Finnish individuals with low or high HDL-C (n=450). APPROACH AND RESULTS: In the pathway analysis of genetic data, we demonstrate that genetic variants within inflammatory pathways were enriched among low HDL-C associated single-nucleotide polymorphisms, and the expression of these pathways upregulated in the adipose tissue of low HDL-C subjects. The lipidomic analysis highlighted the change in HDL particle quality toward putatively more inflammatory and less vasoprotective state in subjects with low HDL-C, as evidenced by their decreased antioxidative plasmalogen contents. We show that the focal point of these inflammatory pathways seems to be the HLA region with its low HDL-associated alleles also associating with more abundant local transcript levels in adipose tissue, increased plasma vascular cell adhesion molecule 1 (VCAM1) levels, and decreased HDL particle plasmalogen contents, markers of adipose tissue inflammation, vascular inflammation, and HDL antioxidative potential, respectively. In a population-based look-up of the inflammatory pathway single-nucleotide polymorphisms in a large Finnish cohorts (n=11 211), no association of the HLA region was detected for HDL-C as quantitative trait, but with extreme HDL-C phenotypes, implying the presence of low or high HDL genes in addition to the population-genomewide association studies-identified HDL genes. CONCLUSIONS: Our study highlights the role of inflammation with a genetic component in subjects with low HDL-C and identifies novel cis-expression quantitative trait loci (cis-eQTL) variants in HLA region to be associated with low HDL-C., Funding agencies:Finnish Foundation for Cardiovascular ResearchNovo Nordisk FoundationHelsinki University Central Hospital Research FoundationEmil Aaltonen FoundationFinnish Medical FoundationBiomedicum Helsinki FoundationAarne Koskelo FoundationFinska LakaresallskapetResearch Council for the HealthAcademy of Finland 132625Paavo Nurmi Foundation
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- 2013
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47. HDL subspecies : association with low HDL-C, obesity, and metabolic syndrome
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Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Division of Cardiology, Söderlund, Sanni, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Division of Cardiology, and Söderlund, Sanni
- Abstract
AIMS An independent, powerful coronary heart disease (CHD) predictor is a low level of high-density lipoprotein cholesterol (HDL-C). Discoidal preβ-HDL particles and large HDL2 particles are the primary cholesterol acceptors in reverse cholesterol transport, a key anti-atherogenic HDL mechanism. The quality of HDL subspecies may provide better markers of HDL functionality than does HDL-C alone. We aimed I) to study whether alterations in the HDL subspecies profile exist in low-HDL-C subjects II) to explore the relationship of any changes in HDL subspecies profile in relation to atherosclerosis and metabolic syndrome; III) to elucidate the impact of genetics and acquired obesity on HDL subspecies distribution. SUBJECTS The study consisted of 3 cohorts: A) Finnish families with low HDL-C and premature CHD (Study I: 67 subjects with familial low HDL-C and 64 controls; Study II: 83 subjects with familial low HDL-C, 65 family members with normal HDL-C, and 133 controls); B) a cohort of 113 low- and 133 high-HDL-C subjects from the Health 2000 Health Examination Survey carried out in Finland (Study III); and C) a Finnish cohort of healthy young adult twins (52 monozygotic and 89 dizygotic pairs) (Study IV). RESULTS AND CONCLUSIONS The subjects with familial low HDL-C had a lower preβ-HDL concentration than did controls, and the low-HDL-C subjects displayed a dramatic reduction (50-70%) in the proportion of large HDL2b particles. The subjects with familial low HDL-C had increased carotid atherosclerosis measured as intima-media-thickness (IMT), and HDL2b particles correlated negatively with IMT. The reduction in both key cholesterol acceptors, preβ-HDL and HDL2 particles, supports the concept of impaired reverse cholesterol transport contributing to the higher CHD risk in low-HDL-C subjects. The family members with normal HDL-C and the young adult twins with acquired obesity showed a reduction in large HDL2 particles and an increase in small HDL3 particles, which may be th, Pieni HDL-kolesterolin määrä on sepelvaltimotaudin vaaratekijä. Monimuotoiset HDL-hiukkaset suojaavat verisuonia mm. kuljettaen ylimääräistä kolesterolia soluista maksaan. HDL-hiukkasten jakauma ja laatu saattavat vaikuttaa siihen, miten hyvin HDL-hiukkaset suojaavat sepelvaltimotaudilta. Tämän tutkimuksen tavoitteet olivat selvittää I) onko henkilöillä, joilla on matala HDL-kolesterolin pitoisuus, muutoksia HDL-hiukkasten jakaumassa, II) liittyvätkö mahdolliset muutokset valtimonkovettumatautiin ja metaboliseen oireyhtymään, III) perimän ja ylipainon vaikutus HDL-hiukkasten jakaumaan. Tutkimus koostui kolmesta kohortista: A) suomalaisista perheistä, joissa esiintyy matalaa HDL-kolesterolin pitoisuutta ja sepelvaltimotautia varhaisella iällä (osatutkimus I: 67 perheenjäsentä, joilla on matala HDL-kolesterolin pitoisuus sekä 64 tervettä verrokkia, osatutkimus II: 83 perheenjäsentä, joilla on matala HDL-kolesterolin pitoisuus, 65 perheenjäsentä, joilla on normaali HDL-kolesterolin pitoisuus, sekä 133 tervettä verrokkia), B) suomalaisesta Terveys 2000 tutkimuksesta (113 henkilöä, joilla on matala HDL-kolesterolin pitoisuus ja 133 henkilöä, joilla on korkea HDL-kolesterolin pitoisuus), C) suomalaisista, nuorista aikuisista kaksosista (52 identtistä ja 89 epäidenttistä paria). Tutkimuksessa todettiin, että henkilöillä, joilla on perinnöllinen matala HDL-kolesterolin pitoisuus, on verrokkeihin nähden pienempi kiekkomaisten preβ-HDL-hiukkasten pitoisuus. Isojen, pyöreiden HDL2b-hiukkasten suhteellinen määrä oli huomattavasti pienentynyt (50-70%) ja pienten HDL3-hiukkasten osuus suurentunut henkilöillä, joilla on matala HDL-kolesterolin pitoisuus. Henkilöillä, joilla on perinnöllinen matala HDL-kolesterolin pitoisuus, kaulavaltimoiden seinämät olivat paksuuntuneet heijastaen heidän sepelvaltimotautiriskiään. HDL2b-hiukkasten osuus oli käänteisesti yhteydessä kaulavaltimoiden seinämäpaksuuteen. HDL2b- ja preβ-HDL-hiukkaset ovat ensisijaisia kolesterolin vastaanottajia soluis
- Published
- 2011
48. Effect of HDL composition and particle size on the resistance of HDL to the oxidation
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University of Helsinki, Research Programs Unit, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Shuhei, Nakanishi, Söderlund, Sanni, Jauhiainen, Matti, Taskinen, Marja-Riitta, University of Helsinki, Research Programs Unit, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Shuhei, Nakanishi, Söderlund, Sanni, Jauhiainen, Matti, and Taskinen, Marja-Riitta
- Published
- 2010
49. Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol
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Yetukuri, Laxman, Söderlund, Sanni, Koivuniemi, Artturi, Seppänen-Laakso, Tuulikki, Niemelä, Perttu S., Hyvönen, Marja, Taskinen, Marja-Riitta, Vattulainen, Ilpo, Jauhiainen, Matti, Oresic, Matej, Yetukuri, Laxman, Söderlund, Sanni, Koivuniemi, Artturi, Seppänen-Laakso, Tuulikki, Niemelä, Perttu S., Hyvönen, Marja, Taskinen, Marja-Riitta, Vattulainen, Ilpo, Jauhiainen, Matti, and Oresic, Matej
- Abstract
A low level of high density lipoprotein cholesterol (HDL-C) is a powerful risk factor for cardiovascular disease. However, despite the reported key role of apolipo-proteins, specifically, apoA-I, in HDL metabolism, lipid molecular composition of HDL particles in subjects with high and low HDL-C levels is currently unknown. Here lipidomics was used to study HDL derived from well-characterized high and low HDL-C subjects. Low HDL-C subjects had elevated triacylglycerols and diminished lysophosphatidylcholines and sphingomyelins. Using information about the lipid composition of HDL particles in these two groups, we reconstituted HDL particles in silico by performing large-scale molecular dynamics simulations. In addition to confirming the measured change in particle size, we found that the changes in lipid composition also induced specific spatial distributions of lipids within the HDL particles, including a higher amount of triacylglycerols at the surface of HDL particles in low HDL-C subjects. Our findings have important implications for understanding HDL metabolism and function. For the first time we demonstrate the power of combining molecular profiling of lipoproteins with dynamic modeling of lipoprotein structure., Funding agencies:European Union FP7-KBBE-222639 Finnish Heart Foundation Sigrid Juselius Foundation Helsinki University Central Hospital Research Foundation
- Published
- 2010
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50. Genomic, Transcriptomic, and Lipidomic Profiling Highlights the Role of Inflammation in Individuals With Low High-density Lipoprotein Cholesterol
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Laurila, Pirkka-Pekka, primary, Surakka, Ida, additional, Sarin, Antti-Pekka, additional, Yetukuri, Laxman, additional, Hyötyläinen, Tuulia, additional, Söderlund, Sanni, additional, Naukkarinen, Jussi, additional, Tang, Jing, additional, Kettunen, Johannes, additional, Mirel, Daniel B., additional, Soronen, Jarkko, additional, Lehtimäki, Terho, additional, Ruokonen, Aimo, additional, Ehnholm, Christian, additional, Eriksson, Johan G., additional, Salomaa, Veikko, additional, Jula, Antti, additional, Raitakari, Olli T., additional, Järvelin, Marjo-Riitta, additional, Palotie, Aarno, additional, Peltonen, Leena, additional, Orešič, Matej, additional, Jauhiainen, Matti, additional, Taskinen, Marja-Riitta, additional, and Ripatti, Samuli, additional
- Published
- 2013
- Full Text
- View/download PDF
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