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4. Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids

Author

Gürdeniz, Gözde, Uusitupa, Matti, Hermansen, Kjeld, Savolainen, Markku J., Schwab, Ursula, Kolehmainen, Marjukka, Brader, Lea, Cloetens, Lieselotte, Herzig, Karl-Heinz, Hukkanen, Janne, Rosqvist, Fredrik, Ulven, Stine Marie, Gunnarsdóttir, Ingibjörg, Thorsdottir, Inga, Oresic, Matej, Poutanen, Kaisa S., Risérus, Ulf, Åkesson, Björn, and Dragsted, Lars Ove

Published
2022
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6. Impact of RYGB surgery on plasma immunoglobulins: association between blood pressure and glucose levels six months after surgery

Author

Happonen, Natalie, primary, Härma, Mari‐Anne, additional, Akhi, Ramin, additional, Nissinen, Antti E., additional, Savolainen, Markku J., additional, Ruuth, Maija, additional, Öörni, Katariina, additional, Adeshara, Krishna, additional, Lehto, Markku, additional, Groop, Per‐Henrik, additional, Koivukangas, Vesa, additional, Hukkanen, Janne, additional, and Hörkkö, Sohvi, additional

Published
2023
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8. Impact of RYGB surgery on plasma immunoglobulins: association between blood pressure and glucose levels six months after surgery.

Author

Happonen, Natalie, Härma, Mari‐Anne, Akhi, Ramin, Nissinen, Antti E., Savolainen, Markku J., Ruuth, Maija, Öörni, Katariina, Adeshara, Krishna, Lehto, Markku, Groop, Per‐Henrik, Koivukangas, Vesa, Hukkanen, Janne, and Hörkkö, Sohvi

Subjects
BLOOD sugar, BACTERIAL antibodies, DIASTOLIC blood pressure, CHEMILUMINESCENCE immunoassay, SURGERY, BLOOD pressure, IMMUNOGLOBULIN M, IMMUNOGLOBULINS, HYPERGLYCEMIA
Abstract

We aimed to study levels of natural antibodies in plasma, and their associations to clinical and fecal biomarkers, before and 6 months after Roux‐en‐Y gastric bypass (RYGB) surgery. Thirty individuals with obesity [16 type 2 diabetic, 14 non‐diabetic (ND)] had RYGB surgery. Total plasma IgA, IgG and IgM antibody levels and specific antibodies to oxidized low‐density lipoprotein (oxLDL), malondialdehyde‐acetaldehyde adducts, Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44), and phosphocholine were measured using chemiluminescence immunoassay. Associations between plasma and fecal antibodies as well as clinical markers were analyzed. RYGB surgery reduced blood pressure, and the glycemic state was improved. A higher level of diastolic blood pressure was associated with lower plasma antibodies to oxLDL after surgery. Also, lower level of glucose markers associated with lower level of plasma antibodies to bacterial virulence factors. Antibodies to oxLDL decreased after surgery, and positive association between active serum lipopolysaccharide and specific oxLDL antibodies was detected. Total IgG levels decreased after surgery, but only in ND individuals. Reduced level of total plasma IgG, improved state of hypertension and hyperglycemia and their associations with decreased levels of specific antibodies in plasma, suggest an improved state of systemic inflammation after RYGB surgery. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Arctic Monitoring and Assessment Programme (AMAP)—IPY Meeting in Iqaluit, Nunavut, Canada (June 2009), and AMAP Human Health Assessment 2009

Author

Hansen, Jens C., Van Oostdam, Jay, Gilman, Andrew P., Odland, Jon Øyvind, Donaldson, Shawn G., Vaktskjold, Arild, Tikhonov, Constantine, Dudarev, Alexey A., Ayotte, Pierre, Berner, James E., Bonefeld-Jørgensen, Eva Cecilie, Carlsen, Anders, Deutch, Bente, Dewailly, Eric, Furgal, Christopher, Muckle, Gina, Ólafsdóttir, Kristín, Pedersen, Henning Sloth, Rautio, Arja, Sandanger, Torkjel M., Weihe, Pal, Weber, Jean-Phillipe, Savolainen, Markku, Skinner, Kelly, Kallenborn, Roland, Series editor, di Prisco, Guido, Series editor, Walton, David, Series editor, and Barr, Susan, Series editor

Published
2016
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11. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Author

Hamann, Andreas, Barakat, Alain, Blüher, Matthias, Linn, Thomas, Mölle, Andrea, Segner, Alexander, Stübler, Petra, Tosch-Sisting, Regina, Pacini, Furio, Santini, Ferruccio, Marchesini, Giulio, Rotella, Carlo Maria, Invitti, Cecilia, Vettor, Roberto, Buscemi, Silvio, Raya, Pedro Mezquita, Freijoo, Felipe Casanueva, de Barbará, Ramón Gomis, Carraro, Raffaele, Bobillo, Enrique Romero, de la Cuesta, Carmen, Farsang, Csaba, Csaszar, Albert, Zahorska-Markiewicz, Barbara, Pupek-Musialik, Danuta, Franek, Edward, Ostrowska, Lucyna, Olszanecka-Glinianowicz, Magdalena, Lalic, Nebojsa, Micic, Dragan, Ludvik, Bernhard, Paulweber, Bernhard, Prager, Rudolf, Scheen, André, Van Gaal, Luc, Astrup, Arne Vernon, Hermansen, Kjeld, Madsbad, Sten, Rissanen, Aila, Nieminen, Sakari, Savolainen, Markku, Krempf, Michel, Romon, Monique, Laville, Martine, Marre, Michel, Mira, Reginald, Finucane, Francis, Veenendaal, Aletha, van Berkum, Frank, Johannsson-Vidarsdóttir, Solrun, Van de Walle, Vivienne, Meesters, Eelco, Hjelmesæth, Jøran, Klemsdal, Tor Ole, Kulseng, Bård, Bach-Kliegel, Birgit, Laederach, Kurt, Villiger, Lukas, Golay, Alain, Bilz, Stefan, Sathyapalan, Thozhukat, Bain, Stephen, Kumar, Sudesh, Le Roux, Carel Wynard, Lean, Michael E.J., McGowan, Barbara, Rehman, Tariq, Wilding, John, Wittert, Gary, Caterson, Ian, Proietto, Joeseph, Prins, John, Neto, Bruno Geloneze, Gross, Jorge Luiz, Chacra, Antonio Roberto, Halpern, Alfredo, de Almeida Suplicy, Henrique, Chow, Francis Chun Chung, Thacker, Hemant P, Chadha, Manoj, Chandalia, Hemaraj, Unnikrishnan, Ambika, Kalra, Sanjay, Deshpande, Neeta, Shunmugavelu, Minakshi, Deshmukh, Vaishali Chetan, Maislos, Maximo, Lieberman, Gabriella Segal, Shimon, Ilan, Stern, Naftali, Nabriski, Dan, Karnieli, Eddy, Shehadeh, Naim, Gonzalez-Galvez, Guillermo, del Rosario Arechavaleta-Granell, Maria, Ortiz, Rafael Margarito Violante, Franco, Guadalupe Morales, Gurieva, Irina, Suplotova, Lyudmila Aleksandrovna, Troshina, Ekaterina, Ruyatkina, Ludmila Aleksandrovna, Voychik, Emma Anatolievna, Martsevich, Sergey, Startseva, Maria A, Seeber, Mary Elizabeth, Badat, Aysha, Ellis, Graham, Altuntas, Yuksel, Guler, Serdar, Ulgen, Ender, Delibasi, Tuncay, Chetty, Tony, Hart, Randy, Janzen, Jeannette, Labonte, Isabelle, Lau, David, Liutkus, Joanne, O'Keefe, Dennis, Padwal, Raj, Ransom, Thomas P.P., Tytus, Richard, Weisnagel, Stanley John, Adler, Jay, Aqua, Keith, Aronoff, Stephen L, Bedel, Gary W., Blevins, Thomas Craig, Blumenau, Joe, Brockmyre, Andrew Peter, Call, Robert S, Canadas, Rafael, Chaykin, Louis B, Cohen, Kenneth, Conrow, Jeffrey Keith, Davis, Matthew G, Downey, H Jackson, Drosman, Steven Richard, Duckor, Steven, Farmer, H. Frank, Farrell, James, Fehnel, Stephen, Finneran, Matthew Patrick, Forbes, Ray, Forker, Alan, Fredrick, Mark, Fujioka, Ken, Geller, Steven Andrew, Gill, Santosh, Glaser, Linda, Greco, Susan Neims, Greenway, Frank Lyons, Harper, Wayne, Herman, Lee, Hoekstra, John, Ingebretsen, Richard, Ison, Rodney, Jain, Rajeev K, Kaplan, Roy, Kaster, Steven Richard, Haase, Gregory A, Kerzner, Boris, Kirstein, Judith Lee, Koltun, William, Krieger, Diane R, Lewis, Cora Elizabeth, Madder, Robert, Marple, Richard N, McDermott, Edward J, Mello, Curtis John, Miller, Alan B., Mullen, Julie, Nardandrea, John, O'Neil, Patrick, Pi-Sunyer, F. Xavier, Pucillo, Ronald M, Rhee, Chanhaeng, Redrick, Scott, Pardini, Aaron, Rothman, Jeffrey, Rubino, Domenica Marie, Sellers, Gladstone, Smith, Timothy, Byars, William David, Soufer, Joseph, Sussman, Allen Michael, Patrick, Kyle, Schramm, Erich Lloyd, Van Cleeff, Martin, Berg, Saul Reuel, Wyatt, Holly Roxanna, Simon, James Alan, le Roux, Carel W, Astrup, Arne, Greenway, Frank, Lau, David C W, Ortiz, Rafael Violante, Wilding, John P H, Skjøth, Trine V, Manning, Linda Shapiro, and Pi-Sunyer, Xavier

Published
2017
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13. Epidemiology: Disease Associations and Modulators of HDL-Related Biomarkers

Author

Savolainen, Markku J., Rosenthal, Walter, Editor-in-chief, Barrett, James E., Series editor, Flockerzi, Veit, Series editor, Frohman, Michael A., Series editor, Geppetti, Pierangelo, Series editor, Hofmann, Franz B., Series editor, Michel, Martin C., Series editor, Moore, Philip, Series editor, Page, Clive P., Series editor, Thorburn, Andrew M., Series editor, Wang, KeWei, Series editor, von Eckardstein, Arnold, editor, and Kardassis, Dimitris, editor

Published
2015
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17. Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome

Author

Kolehmainen, Marjukka, Ulven, Stine M, Paananen, Jussi, de Mello, Vanessa, Schwab, Ursula, Carlberg, Carsten, Myhrstad, Mari, Pihlajamäki, Jussi, Dungner, Elisabeth, Sjölin, Eva, Gunnarsdottir, Ingibjörg, Cloetens, Lieselotte, Landin-Olsson, Mona, Akesson, Björn, Rosqvist, Fredrik, Hukkanen, Janne, Herzig, Karl-Heinz, Dragsted, Lars O, Savolainen, Markku J, Brader, Lea, Hermansen, Kjeld, Risérus, Ulf, Thorsdottir, Inga, Poutanen, Kaisa S, Uusitupa, Matti, Arner, Peter, and Dahlman, Ingrid

Published
2015
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20. Specific collagen XVIII isoforms promote adipose tissue accrual via mechanisms determining adipocyte number and affect fat deposition

Author

Aikio, Mari, Elamaa, Harri, Vicente, David, Izzi, Valerio, Kaur, Inderjeet, Seppinen, Lotta, Speedy, Helen E., Kaminska, Dorota, Kuusisto, Sanna, Sormunen, Raija, Heljasvaara, Ritva, Jones, Emma L., Muilu, Mikko, Jauhiainen, Matti, Pihlajamäki, Jussi, Savolainen, Markku J., Shoulders, Carol C., and Pihlajaniemi, Taina

Published
2014
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21. Arctic Monitoring and Assessment Programme (AMAP)—IPY Meeting in Iqaluit, Nunavut, Canada (June 2009), and AMAP Human Health Assessment 2009

Author

Hansen, Jens C., primary, Van Oostdam, Jay, additional, Gilman, Andrew P., additional, Odland, Jon Øyvind, additional, Donaldson, Shawn G., additional, Vaktskjold, Arild, additional, Tikhonov, Constantine, additional, Dudarev, Alexey A., additional, Ayotte, Pierre, additional, Berner, James E., additional, Bonefeld-Jørgensen, Eva Cecilie, additional, Carlsen, Anders, additional, Deutch, Bente, additional, Dewailly, Eric, additional, Furgal, Christopher, additional, Muckle, Gina, additional, Ólafsdóttir, Kristín, additional, Pedersen, Henning Sloth, additional, Rautio, Arja, additional, Sandanger, Torkjel M., additional, Weihe, Pal, additional, Weber, Jean-Phillipe, additional, Savolainen, Markku, additional, and Skinner, Kelly, additional

Published
2016
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24. Effects of a healthy Nordic diet on plasma 25-hydroxyvitamin D concentration in subjects with metabolic syndrome: a randomized, placebo-controlled trial (SYSDIET)

Author

Brader, Lea, Rejnmark, Lars, Carlberg, Carsten, Schwab, Ursula, Kolehmainen, Marjukka, Rosqvist, Fredrik, Cloetens, Lieselotte, Landin-Olsson, Mona, Gunnarsdottir, Ingibjorg, Poutanen, Kaisa S., Herzig, Karl-Heinz, Risérus, Ulf, Savolainen, Markku J., Thorsdottir, Inga, Uusitupa, Matti, and Hermansen, Kjeld

Published
2014
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27. Distinct Fatty Acid Compositions of HDL Phospholipids Are Characteristic of Metabolic Syndrome and Premature Coronary Heart Disease—Family Study

Author

Paavola, Timo, Bergmann, Ulrich, Kuusisto, Sanna, Kakko, Sakari, Savolainen, Markku J., and Salonurmi, Tuire

Subjects
Adult, Male, QH301-705.5, Fatty Acids, Coronary Artery Disease, Middle Aged, Article, metabolic syndrome, Chemistry, Risk Factors, Humans, lipidomics, Family, Female, lipids (amino acids, peptides, and proteins), coronary heart disease, Biology (General), Lipoproteins, HDL, QD1-999, Phospholipids, HDL subfraction, phospholipid, mass spectrometry
Abstract

HDL particles can be structurally modified in atherosclerotic disorders associated with low HDL cholesterol level (HDL-C). We studied whether the lipidome of the main phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin (SM) species of HDL2 and HDL3 subfractions is associated with premature coronary heart disease (CHD) or metabolic syndrome (MetS) in families where common low HDL-C predisposes to premature CHD. The lipidome was analyzed by LC-MS. Lysophosphatidylcholines were depleted of linoleic acid relative to more saturated and shorter-chained acids containing species in MetS compared with non-affected subjects: the ratio of palmitic to linoleic acid was elevated by more than 30%. A minor PC (16:0/16:1) was elevated (28–40%) in MetS. The contents of oleic acid containing PCs were elevated relative to linoleic acid containing PCs in MetS, the ratio of PC (16:0/18:1) to PC (16:0/18:2) was elevated by 11–16%. Certain PC and SM ratios, e.g., PC (18:0/20:3) to PC (16:0/18:2) and a minor SM 36:2 to an abundant SM 34:1, were higher (11–36%) in MetS and CHD. The fatty acid composition of certain LPCs and PCs displayed a characteristic pattern in MetS, enriched with palmitic, palmitoleic or oleic acids relative to linoleic acid. Certain PC and SM ratios related consistently to CHD and MetS.

Published
2021

31. The Gaucher earlier diagnosis consensus point-scoring system (GED-C PSS): Evaluation of a prototype in Finnish Gaucher disease patients and feasibility of screening retrospective electronic health record data for the recognition of potential undiagnosed patients in Finland

Author

Savolainen, Markku J., primary, Karlsson, Antti, additional, Rohkimainen, Samppa, additional, Toppila, Iiro, additional, Lassenius, Mariann I., additional, Falconi, Carlos Vaca, additional, Uusi-Rauva, Kristiina, additional, and Elomaa, Kaisa, additional

Published
2021
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32. Activation of pregnane X receptor induces atherogenic lipids and PCSK9 by a SREBP2‐mediated mechanism

Author

Karpale, Mikko, primary, Käräjämäki, Aki Juhani, additional, Kummu, Outi, additional, Gylling, Helena, additional, Hyötyläinen, Tuulia, additional, Orešič, Matej, additional, Tolonen, Ari, additional, Hautajärvi, Heidi, additional, Savolainen, Markku J., additional, Ala‐Korpela, Mika, additional, Hukkanen, Janne, additional, and Hakkola, Jukka, additional

Published
2021
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34. Activation of nuclear receptor PXR induces atherogenic lipids and PCSK9 through SREBP2-mediated mechanism

Author

Karpale, Mikko, Käräjämäki, Aki Juhani, Kummu, Outi, Gylling, Helena, Hyötyläinen, Tuulia, Oresic, Matej, Tolonen, Ari, Hautajärvi, Heidi, Savolainen, Markku J., Ala-Korpela, Mika, Hukkanen, Janne, Hakkola, Jukka, Karpale, Mikko, Käräjämäki, Aki Juhani, Kummu, Outi, Gylling, Helena, Hyötyläinen, Tuulia, Oresic, Matej, Tolonen, Ari, Hautajärvi, Heidi, Savolainen, Markku J., Ala-Korpela, Mika, Hukkanen, Janne, and Hakkola, Jukka

Abstract

BACKGROUND AND PURPOSE: Many drugs and environmental contaminants induce hypercholesterolemia and promote the risk of atherosclerotic cardiovascular disease. The mechanisms involved are poorly defined precluding efficient prediction and prevention. We tested the hypothesis that pregnane X receptor (PXR), a xenobiotic-sensing nuclear receptor, regulates the level of circulating atherogenic lipids in humans and utilized mouse experiments to identify the mechanisms involved. EXPERIMENTAL APPROACH: We performed serum NMR metabolomics in healthy volunteers administered rifampicin, a prototypical human PXR ligand, or placebo in a crossover setting. Furthermore, we used high-fat diet fed wildtype and PXR knockout mice to investigate the mechanisms and pathways mediating the PXR-induced alterations in cholesterol homeostasis. KEY RESULTS: Activation of PXR induced cholesterogenesis both in pre-clinical and clinical settings. In human volunteers, rifampicin increased IDL, LDL and total cholesterol and lathosterol-cholesterol ratio, a marker of cholesterol synthesis, suggesting increased cholesterol synthesis. Mechanistic studies in mice indicated that PXR activation launches widespread induction of the cholesterol synthesis genes including the rate-limiting Hmgcr and upregulates the intermediates in the Kandutsch-Russell cholesterol synthesis pathway in the liver. Additionally, PXR activation induced plasma PCSK9, a negative regulator of hepatic LDL uptake, in both mice and humans. We propose that these effects were mediated through increased proteolytic activation of SREBP2 in response to PXR activation. CONCLUSION AND IMPLICATIONS: PXR activation induces cholesterol synthesis and elevates LDL and total cholesterol in humans. The PXR-SREBP2 pathway is a novel regulator of the cholesterol and PCSK9 synthesis, and a molecular mechanism for drug- and chemical-induced hypercholesterolemia., Funding Agencies:Sigrid Juselius Foundation Diabetes Research Foundation Northern Finland Health Care Support Foundation Finnish Foundation for Cardiovascular Research Finnish Medical Foundation H2020 Societal Challenges 825762

Published
2021
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35. A Dietary Biomarker Approach Captures Compliance and Cardiometabolic Effects of a Healthy Nordic Diet in Individuals with Metabolic Syndrome1-3

Author

Marklund, Matti, Magnusdottir, Ola K., Rosqvist, Fredrik, Cloetens, Lieselotte, Landberg, Rikard, Kolehmainen, Marjukka, Brader, Lea, Hermansen, Kjeld, Poutanen, Kaisa S., Herzig, Karl-Heinz, Hukkanen, Janne, Savolainen, Markku J., Dragsted, Lars O., Schwab, Ursula, Paananen, Jussi, Uusitupa, Matti, Åkesson, Björn, Thorsdottir, Inga, and Risérus, Ulf

Published
2014
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36. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Couto Alves, Alexessander, De Silva, N Maneka G, Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H Rob, Warrington, Nicole M, Lewin, Alexandra M, Kaakinen, Marika, Cousminer, Diana L, Thiering, Elisabeth, Timpson, Nicholas J, Bond, Tom A, Lowry, Estelle, Brown, Christopher D, Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P, Geller, Frank, Speed, Doug, Coin, Lachlan J M, Loh, Marie, Barton, Sheila J, Beilin, Lawrence J, Bisgaard, Hans, Bønnelykke, Klaus, Alili, Rohia, Hatoum, Ida J, Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clément, Karine, Claringbould, Annique A J, Van Duijn, Cornelia M, Moltchanova, Elena, Eriksson, Johan G, Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M, Freathy, Rachel M, Elliott, Paul, Widén, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T, Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W, Hofman, Albert, Hyppönen, Elina, Inskip, Hazel, Kaplan, Lee M, Hedman, Asa K, Läärä, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A, Lawlor, Debbie A, Melbye, Mads, Ahluwalia, Tarunveer S, Marinelli, Marcella, Millwood, Iona Y, Palmer, Lyle J, Pennell, Craig E, Perry, John R, Ring, Susan M, Savolainen, Markku J, Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M T, Uitterlinden, Andre G, Schierding, William, O'Sullivan, Justin M, Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F, Buxton, Jessica L, Blakemore, Alexandra I F, Ong, Ken K, Jaddoe, Vincent W V, Grant, Struan F A, Sebert, Sylvain, McCarthy, Mark I, Järvelin, Marjo-Riitta, Erasmus MC other, Epidemiology, Internal Medicine, Pediatrics, Medical Research Council (MRC), Sovio, Ulla [0000-0002-0799-1105], Perry, John [0000-0001-6483-3771], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Warrington, Nicole M [0000-0003-4195-775X], Lewin, Alexandra M [0000-0003-0081-7582], Kaakinen, Marika [0000-0002-9228-0462], Cousminer, Diana L [0000-0001-8864-7893], Timpson, Nicholas J [0000-0002-7141-9189], Lowry, Estelle [0000-0002-4655-416X], Brown, Christopher D [0000-0002-3785-5008], Estivill, Xavier [0000-0002-0723-2256], Geller, Frank [0000-0002-9238-3269], Speed, Doug [0000-0002-0096-9765], Coin, Lachlan J M [0000-0002-4300-455X], Loh, Marie [0000-0003-3626-8466], Barton, Sheila J [0000-0003-4963-4242], Alili, Rohia [0000-0002-0158-4250], Schramm, Katharina [0000-0002-8809-3170], Charles, Marie-Aline [0000-0003-4025-4390], Claringbould, Annique A J [0000-0002-9201-6557], van Duijn, Cornelia M [0000-0002-2374-9204], Feenstra, Bjarke [0000-0003-1478-649X], Frayling, Timothy M [0000-0001-8362-2603], Freathy, Rachel M [0000-0003-4152-2238], Widén, Elisabeth [0000-0001-7108-2806], Hakonarson, Hakon [0000-0003-2814-7461], Rodriguez, Alina [0000-0003-1209-8802], Heude, Barbara [0000-0002-1565-1629], Holloway, John W [0000-0001-9998-0464], Hofman, Albert [0000-0002-9865-121X], Hyppönen, Elina [0000-0003-3670-9399], Inskip, Hazel [0000-0001-8897-1749], Kaplan, Lee M [0000-0002-6301-2696], Prokisch, Holger [0000-0003-2379-6286], Lakka, Timo A [0000-0002-9199-2871], Lawlor, Debbie A [0000-0002-6793-2262], Melbye, Mads [0000-0001-8264-6785], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Marinelli, Marcella [0000-0002-5450-3960], Palmer, Lyle J [0000-0002-1628-3055], Pennell, Craig E [0000-0002-0937-6165], Perry, John R [0000-0001-6483-3771], Ring, Susan M [0000-0003-3103-9330], Savolainen, Markku J [0000-0002-2557-6423], Rivadeneira, Fernando [0000-0001-9435-9441], Sunyer, Jordi [0000-0002-2602-4110], Schierding, William [0000-0001-5659-2701], O'Sullivan, Justin M [0000-0003-2927-450X], Prokopenko, Inga [0000-0003-1624-7457], Smith, George Davey [0000-0002-1407-8314], Felix, Janine F [0000-0002-9801-5774], Ong, Ken K [0000-0003-4689-7530], Jaddoe, Vincent W V [0000-0003-2939-0041], Sebert, Sylvain [0000-0001-6681-6983], McCarthy, Mark I [0000-0002-4393-0510], and Järvelin, Marjo-Riitta [0000-0002-2149-0630]

Subjects
Adult, Male, Pharmacogenomic Variants, Quantitative Trait Loci, BLOOD-PRESSURE, 030209 endocrinology & metabolism, Polymorphism, Single Nucleotide, Body Mass Index, EARLY-LIFE, 03 medical and health sciences, AGE, Quantitative Trait, Heritable, 0302 clinical medicine, Humans, Genetic Predisposition to Disease, Longitudinal Studies, 030212 general & internal medicine, GENOME-WIDE ASSOCIATION, METABOLIC RISK, Growth Charts, FTO GENE, Child, Research Articles, Genetic Association Studies, Adaptor Proteins, Signal Transducing, 2. Zero hunger, Science & Technology, BIRTH COHORT, Intracellular Signaling Peptides and Proteins, nutritional and metabolic diseases, SciAdv r-articles, Infant, Human Genetics, Genomics, 3. Good health, Multidisciplinary Sciences, BODY-MASS INDEX, OBESITY, Science & Technology - Other Topics, Receptors, Leptin, ADIPOSITY, Female, biological, Research Article, Genome-Wide Association Study
Abstract

Longitudinal data find a new variant controlling BMI in infancy and reveal genetic differences between infant and adult BMI., Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Published
2019

38. 4β-Hydroxycholesterol Signals From the Liver to Regulate Peripheral Cholesterol Transporters.

Author

Salonurmi, Tuire, Nabil, Heba, Ronkainen, Justiina, Hyötyläinen, Tuulia, Hautajärvi, Heidi, Savolainen, Markku J, Tolonen, Ari, Oresic, Matej, Känsäkoski, Päivi, Rysä, Jaana, Hakkola, Jukka, Hukkanen, Janne, Salonurmi, Tuire, Nabil, Heba, Ronkainen, Justiina, Hyötyläinen, Tuulia, Hautajärvi, Heidi, Savolainen, Markku J, Tolonen, Ari, Oresic, Matej, Känsäkoski, Päivi, Rysä, Jaana, Hakkola, Jukka, and Hukkanen, Janne

Abstract

Activation of pregnane X receptor (PXR) elevates circulating 4β-hydroxycholesterol (4βHC), an agonist of liver X receptor (LXR). PXR may also regulate 25-hydroxycholesterol and 27-hydroxycholesterol. Our aim was to elucidate the roles of PXR and oxysterols in the regulation of cholesterol transporters. We measured oxysterols in serum of volunteers dosed with PXR agonist rifampicin 600 mg/day versus placebo for a week and analyzed the expression of cholesterol transporters in mononuclear cells. The effect of 4βHC on the transport of cholesterol and the expression of cholesterol transporters was studied in human primary monocyte-derived macrophages and foam cells in vitro. The expression of cholesterol transporters was measured also in rat tissues after dosing with a PXR agonist. The levels of 4βHC were elevated, while 25-hydroxycholesterol and 27-hydroxycholesterol remained unchanged in volunteers dosed with rifampicin. The expression of ATP binding cassette transporter A1 (ABCA1) was induced in human mononuclear cells in vivo. The influx of cholesterol was repressed by 4βHC, as was the expression of influx transporter lectin-like oxidized LDL receptor-1 in vitro. The cholesterol efflux and the expression of efflux transporters ABCA1 and ABCG1 were induced. The expression of inducible degrader of the LDL receptor was induced. In rats, PXR agonist increased circulating 4βHC and expression of LXR targets in peripheral tissues, especially ABCA1 and ABCG1 in heart. In conclusion, PXR activation-elevated 4βHC is a signaling molecule that represses cholesterol influx and induces efflux. The PXR-4βHC-LXR pathway could link the hepatic xenobiotic exposure and the regulation of cholesterol transport in peripheral tissues., Funding Agencies:Academy of Finland 286743 276747Duodecim Society of Oulu Finnish Medical Foundation Finnish Foundation for Cardiovascular Research Northern Finland Health Care Support Foundation Diabetes Research Foundation

Published
2020
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39. Plasma Alkylresorcinols Reflect Important Whole-Grain Components of a Healthy Nordic Diet1-4

Author

Magnusdottir, Ola Kally, Landberg, Rikard, Gunnarsdottir, Ingibjorg, Cloetens, Lieselotte, Åkesson, Björn, Önning, Gunilla, Jonsdottir, Svandis Erna, Rosqvist, Fredrik, Schwab, Ursula, Herzig, Karl-Heinz, Savolainen, Markku J., Brader, Lea, Hermansen, Kjeld, Kolehmainen, Marjukka, Poutanen, Kaisa, Uusitupa, Matti, Thorsdottir, Inga, and Risérus, Ulf

Published
2013
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44. A novel Bayesian approach to quantify clinical variables and to determine their spectroscopic counterparts in 1H NMR metabonomic data

Author

Kaski Kimmo, Hannuksela Minna L, Savolainen Markku J, Mäkelä Sanna M, Ingman Petri, Soininen Pasi, Mäkinen Ville-Petteri, Vehtari Aki, and Ala-Korpela Mika

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background A key challenge in metabonomics is to uncover quantitative associations between multidimensional spectroscopic data and biochemical measures used for disease risk assessment and diagnostics. Here we focus on clinically relevant estimation of lipoprotein lipids by 1H NMR spectroscopy of serum. Results A Bayesian methodology, with a biochemical motivation, is presented for a real 1H NMR metabonomics data set of 75 serum samples. Lipoprotein lipid concentrations were independently obtained for these samples via ultracentrifugation and specific biochemical assays. The Bayesian models were constructed by Markov chain Monte Carlo (MCMC) and they showed remarkably good quantitative performance, the predictive R-values being 0.985 for the very low density lipoprotein triglycerides (VLDL-TG), 0.787 for the intermediate, 0.943 for the low, and 0.933 for the high density lipoprotein cholesterol (IDL-C, LDL-C and HDL-C, respectively). The modelling produced a kernel-based reformulation of the data, the parameters of which coincided with the well-known biochemical characteristics of the 1H NMR spectra; particularly for VLDL-TG and HDL-C the Bayesian methodology was able to clearly identify the most characteristic resonances within the heavily overlapping information in the spectra. For IDL-C and LDL-C the resulting model kernels were more complex than those for VLDL-TG and HDL-C, probably reflecting the severe overlap of the IDL and LDL resonances in the 1H NMR spectra. Conclusion The systematic use of Bayesian MCMC analysis is computationally demanding. Nevertheless, the combination of high-quality quantification and the biochemical rationale of the resulting models is expected to be useful in the field of metabonomics.

Published
2007
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45. High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis

Author

Würtz, Peter, Raiko, Juho R., Magnussen, Costan G., Soininen, Pasi, Kangas, Antti J., Tynkkynen, Tuulia, Thomson, Russell, Laatikainen, Reino, Savolainen, Markku J., Laurikka, Jari, Kuukasjärvi, Pekka, Tarkka, Matti, Karhunen, Pekka J., Jula, Antti, Viikari, Jorma S., Kähönen, Mika, Lehtimäki, Terho, Juonala, Markus, Ala-Korpela, Mika, and Raitakari, Olli T.

Published
2012
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46. Metabolic Signatures of Insulin Resistance in 7,098 Young Adults

Author

Würtz, Peter, Mäkinen, Ville-Petteri, Soininen, Pasi, Kangas, Antti J., Tukiainen, Taru, Kettunen, Johannes, Savolainen, Markku J., Tammelin, Tuija, Viikari, Jorma S., Rönnemaa, Tapani, Kähönen, Mika, Lehtimäki, Terho, Ripatti, Samuli, Raitakari, Olli T., Järvelin, Marjo-Riitta, and Ala-Korpela, Mika

Published
2012
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47. Detailed metabolic and genetic characterization reveals new associations for 30 known lipid loci

Author

Tukiainen, Taru, Kettunen, Johannes, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Sarin, Antti-Pekka, Tikkanen, Emmi, OʼReilly, Paul F., Savolainen, Markku J., Kaski, Kimmo, Pouta, Anneli, Jula, Antti, Lehtimäki, Terho, Kähönen, Mika, Viikari, Jorma, Taskinen, Marja-Riitta, Jauhiainen, Matti, Eriksson, Johan G., Raitakari, Olli, Salomaa, Veikko, Järvelin, Marjo-Riitta, Perola, Markus, Palotie, Aarno, Ala-Korpela, Mika, and Ripatti, Samuli

Published
2012
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50. Lifestyle counselling by persuasive information and communications technology reduces prevalence of metabolic syndrome in a dose–response manner: a randomized clinical trial (PrevMetSyn)

Author

Seo, Young-Gyun, primary, Salonurmi, Tuire, additional, Jokelainen, Terhi, additional, Karppinen, Pasi, additional, Teeriniemi, Anna-Maria, additional, Han, Junhee, additional, Park, Kyung Hee, additional, Oinas-Kukkonen, Harri, additional, and Savolainen, Markku J., additional

Published
2020
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