A5042831400- Liver Disease Diagnosis and Treatment
- Diet, Metabolism, and Disease
- Liver Disease and Transplantation
- Lipid metabolism and biosynthesis
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- Alcohol Consumption and Health Effects
- Liver Diseases and Immunity
- Lipid metabolism and disorders
- Gut microbiota and health
- Adipose Tissue and Metabolism
- Hepatitis C virus research
- Fatty Acid Research and Health
- Metabolism, Diabetes, and Cancer
- Hormonal Regulation and Hypertension
- Genomics and Phylogenetic Studies
- Peroxisome Proliferator-Activated Receptors
- Hepatocellular Carcinoma Treatment and Prognosis
- Spectroscopy Techniques in Biomedical and Chemical Research
- Metabolomics and Mass Spectrometry Studies
- Metabolism and Genetic Disorders
- Genetic and Kidney Cyst Diseases
- Pediatric Hepatobiliary Diseases and Treatments
- Nuclear Structure and Function
- Muscle metabolism and nutrition
Minerva Foundation
2016-2025
Helsinki University Hospital
2016-2025
University of Helsinki
2016-2025
Yale University
2019-2024
University of New Haven
2023
Klinikum rechts der Isar
2022
Technical University of Munich
2022
University of California, San Diego
2022
OBJECTIVE Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis hepatic de novo lipogenesis (DNL) are the main pathways contributing IHTG. We hypothesized that dietary macronutrient composition influences pathways, mediators, magnitude of weight gain-induced changes in RESEARCH DESIGN AND METHODS overfed 38 overweight subjects (age 48 ± years, BMI 31 1 kg/m2, fat 4.7...
The use of relative abundance data from next generation sequencing (NGS) can lead to misinterpretations microbial community structures, as the increase one taxon leads concurrent decrease other(s) in compositional data. Although different DNA- and cell-based methods well statistical approaches have been developed overcome compositionality problem, biological relevance absolute bacterial abundances has demonstrated, human microbiome research not yet adopted these methods, likely due...
Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation pathology of non-alcoholic fatty liver disease (NAFLD). However, underlying mechanisms linking EC exposure with NAFLD remain poorly understood there is no data on their impact human metabolome. Herein, we hypothesized ECs, particularly perfluorinated alkyl substances (PFAS), impacts metabolism, specifically bile acid metabolism.In a well-characterized...
Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified acids (NEFA), the main substrate for synthesis intrahepatic triglycerides (IHTG). To explore underlying mechanism, we quantified hepatic mitochondrial fluxes their regulators humans using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope...
There is substantial inter-individual variability in the risk of non-alcoholic fatty liver disease (NAFLD). Part which explained by insulin resistance (IR) ('MetComp') and part common modifiers genetic ('GenComp'). We examined how IR on one hand other contribute to pathogenesis NAFLD.
Fatty liver disease (FLD) is a growing epidemic that expected to be the leading cause of end-stage within next decade. Both environmental and genetic factors contribute susceptibility FLD. Several variants contributing FLD have been identified in exome-wide association studies. However, there still missing hereditability indicating other are yet discovered.To find genes involved FLD, we first examined missense nonsense with alanine aminotransferase at an level 425,671 participants from UK...
The common patatin-like phospholipase domain–containing protein 3 (PNPLA3) variant I148M predisposes to nonalcoholic liver disease but not its metabolic sequelae. We compared the handling of labeled polyunsaturated fatty acids (PUFAs) and saturated (SFA) in vivo humans cells harboring different PNPLA3 genotypes. In 148M homozygous individuals, triglycerides (TGs) very low–density lipoproteins (VLDL) were depleted PUFAs both under fasting postprandial conditions with 148I homozygotes,...
Objective Non-alcoholic fatty liver disease (NAFLD) is a common prelude to cirrhosis and hepatocellular carcinoma. The genetic rs641738 C>T variant in the lysophosphatidylinositol acyltransferase 1 ( LPIAT1)/membrane bound O-acyltransferase domain-containing 7 , which incorporates arachidonic acid into phosphatidylinositol (PI), associated with entire spectrum of NAFLD. In this study, we investigated mechanism underlying association mice cultured human hepatocytes. Design We generated...
Carriers of the hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) gene variant (rs72613567:TA) have a reduced risk NASH and cirrhosis but not steatosis. We determined its effect on liver histology, lipidome, transcriptome using ultra performance liquid chromatography-mass spectrometry RNA-seq. In carriers noncarriers variant, we also measured pathways hepatic fatty acids (de novo lipogenesis [DNL] adipose tissue lipolysis [ATL] 2H2O 2H-glycerol) insulin sensitivity 3H-glucose...
Current screening strategies for chronic liver disease focus on detection of subclinical advanced fibrosis but cannot identify those at high future risk severe disease. Our aim was to develop and validate a prediction model incident in the general population based widely available factors.Multivariable Cox regression analyses were used models liver-related outcomes with without laboratory measures (Modellab Modelnon-lab) 25,760 individuals aged 40-70 years. Their data sourced from Finnish...
BACKGROUNDA pilot, single-center study showed that first-degree relatives of probands with nonalcoholic fatty liver disease (NAFLD) cirrhosis have a high risk advanced fibrosis. We aimed to validate these findings using 2 independent cohorts from the US and Europe.METHODSThis prospective included NAFLD fibrosis, without non-NAFLD, at least 1 relative. A total 396 - 220 in derivation cohort 176 validation were enrolled study, fibrosis was evaluated magnetic resonance elastography other...
The PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but underlying pathophysiology remains unclear. We studied effect this on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, had higher plasma β-hydroxybutyrate concentrations lower de novo lipogenesis (DNL) compared to non-carriers. a mixed meal, acids were channeled toward...
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic disease, in which prognosis determined by fibrosis. A variant hydroxysteroid 17-beta dehydrogenase 13 (
Steatotic liver diseases (SLDs) affect one-third of the population, but pathogenesis underlying these is not well understood, limiting available treatments. A common factor in SLDs increased hepatic mitochondrial reductive stress, which occurs as a result excessive lipid and alcohol metabolism. Recent research has also shown that genetic risk factors contribute to this stress. This review aims explore how increase stress it disrupts metabolism, leading SLDs. Additionally, will discuss latest...
Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity.
Steatotic liver disease (SLD) prevails as the most common chronic yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, mechanistic link between IL-32 intracellular triglyceride metabolism remains be elucidated. We demonstrate vitro that incubation IL-32β protein leads an increase synthesis, while downregulation IL32 by small interfering RNA...