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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; Stahlman, Marcus; Bergh, Per-Olof; Adiels, Martin; Piening, Brian D.; Graner, Marit; Lundbom, Nina; Williams, Kevin J.; Romeo, Stefano; Nielsen, Jens; Snyder, Michael; Uhlen, Mathias; Bergstrom, Goran; Perkins, Rosie; Marschall, Hanns-Ulrich; Backhed, Fredrik; Taskinen, Marja-Riitta; Boren, Jan (2018)
    A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.
  • Åberg, Fredrik; Kantojärvi, Katri; Männistö, Ville; But, Anna; Salomaa, Veikko; Niiranen, Teemu; Färkkilä, Martti; Luukkonen, Panu; Männistö, Satu; Lundqvist, Annamari; Perola, Markus; Jula, Antti (2022)
    Arterial hypertension (HTA) is associated with liver disease, but causality remains unclear. We investigated whether genetic predisposition to HTA is associated with liver disease in the population, and if antihypertensive medication modifies this association. Participants of the Finnish health-examination surveys, FINRISK 1992-2012 and Health 2000 (n = 33,770), were linked with national electronic healthcare registers for liver-related outcomes (K70-K77, C22.0) and with the drug reimbursement registry for new initiation of antihypertensive medication during follow-up. Genetic predisposition to HTA was defined by polygenic risk scores (PRSs). During a median 12.9-year follow-up (409,268.9 person-years), 441 liver-related outcomes occurred. In the fully-adjusted Cox-regression models, both measured systolic blood pressure and clinically defined HTA were associated with liver-related outcomes. PRSs for systolic and diastolic blood pressure were significantly associated with liver-related outcomes (HR/SD 1.19, 95% CI 1.01-1.24, and 1.12, 95% CI 1.01-1.25, respectively). In the highest quintile of the systolic blood pressure PRS, new initiation of antihypertensive medication was associated with reduced rates of liver-related outcomes (HR 0.55, 95% CI 0.31-0.97). HTA and a genetic predisposition for HTA are associated with liver-related outcomes in the population. New initiation of antihypertensive medication attenuates this association in persons with high genetic risk for HTA.
  • Rembeck, Karolina; Maglio, Cristina; Lagging, Martin; Christensen, Peer Brehm; Färkkilä, Martti Antero; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Morch, Kristine; Norkrans, Gunnar; Hellstrand, Kristoffer; Lindh, Magnus; Pirazzi, Carlo; Burza, Maria Antonella; Romeo, Stefano; Westin, Johan; NORDynamIC Grp (2012)