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Träfflista för sökning "WFRF:(Käkelä Pirjo) ;lar1:(lu)"

Sökning: WFRF:(Käkelä Pirjo) > Lunds universitet

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1.
  • de Mello, Vanessa, et al. (författare)
  • Human liver epigenetic alterations in non-alcoholic steatohepatitis are related to insulin action
  • 2017
  • Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 12:4, s. 287-295
  • Tidskriftsartikel (refereegranskat)abstract
    • Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5 ± 7.7 years, BMI: 43 ± 5.7 kg/m2, type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated. Thirty-four individuals had a normal liver phenotype, 35 had simple steatosis, and 26 had NASH. Genome-wide DNA methylation pattern was analyzed using the Infinium HumanMethylation450 BeadChip. mRNA expression was analyzed from 42 individuals using the HumanHT-12 Expression BeadChip. We identified 1,292 CpG sites representing 677 unique genes differentially methylated in liver of individuals with NASH (q < 0.001), independently of T2D, age, sex, and BMI. Focusing on the top-ranking 30 and another 37 CpG sites mapped to genes enriched in pathways of metabolism (q = 0.0036) and cancer (q = 0.0001) all together, 59 NASH-associated CpG sites correlated with fasting insulin levels independently of age, fasting glucose, or T2D. From these, we identified 30 correlations between DNA methylation and mRNA expression, for example LDHB (r = −0.45, P = 0.003). We demonstrated that NASH, more than simple steatosis, associates with differential DNA methylation in the human liver. These epigenetic alterations in NASH are linked with insulin metabolism.
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2.
  • Hyysalo, Jenni, et al. (författare)
  • A population-based study on the prevalence of NASH using scores validated against liver histology.
  • 2014
  • Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278. ; 60:4, s. 839-846
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology.
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3.
  • Mancina, Rosellina Margherita, et al. (författare)
  • The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent.
  • 2016
  • Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 150:5, s. 1219-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7-TMC4 is a susceptibility locus for the development and progression of NAFLD.
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4.
  • Nilsson, Emma A, et al. (författare)
  • Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels.
  • 2015
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:11, s. 1491-1501
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigenetic variation may contribute to the development of complex metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a hallmark of T2D. However, it remains unknown if epigenetic alterations take place in the liver from diabetic subjects. Therefore, we investigated the genome-wide DNA methylation pattern in the liver from subjects with T2D and non-diabetic controls and related epigenetic alterations to gene expression and circulating folate levels.
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5.
  • Sehgal, Ratika, et al. (författare)
  • Liver saturated fat content associates with hepatic DNA methylation in obese individuals
  • 2023
  • Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Accumulation of saturated fatty acids (SFAs) in the liver is known to induce hepatic steatosis and inflammation causing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although SFAs have been shown to affect the epigenome in whole blood, pancreatic islets, and adipose tissue in humans, and genome-wide DNA methylation studies have linked epigenetic changes to NAFLD and NASH, studies focusing on the association of SFAs and DNA methylation in human liver are missing. We, therefore, investigated whether human liver SFA content associates with DNA methylation and tested if SFA-linked alterations in DNA methylation associate with NAFLD-related clinical phenotypes in obese individuals. Results: We identified DNA methylation (Infinium HumanMethylation450 BeadChip) of 3169 CpGs to be associated with liver total SFA content (q-value < 0.05) measured using proton NMR spectroscopy in participants of the Kuopio Obesity Surgery Study (n = 51; mean ± SD:49.3 ± 8.5 years old; BMI:43.7 ± 6.2 kg/m2). Of these 3169 sites, 797 overlapped with previously published NASH-associated CpGs (NASH-SFA), while 2372 CpGs were exclusively associated with SFA (Only-SFA). The corresponding annotated genes of these only-SFA CpGs were found to be enriched in pathways linked to satiety and hunger. Among the 54 genes mapping to these enriched pathways, DNA methylation of CpGs mapping to PRKCA and TSPO correlated with their own mRNA expression (HumanHT-12 Expression BeadChip). In addition, DNA methylation of another ten of these CpGs correlated with the mRNA expression of their neighboring genes (p value < 0.05). The proportion of CpGs demonstrating a correlation of DNA methylation with plasma glucose was higher in NASH-SFA and only-SFA groups, while the proportion of significant correlations with plasma insulin was higher in only-NASH and NASH-SFA groups as compared to all CpGs on the Illumina 450 K array (Illumina, San Diego, CA, USA). Conclusions: Our results suggest that one of the mechanisms how SFA could contribute to metabolic dysregulation in NAFLD is at the level of DNA methylation. We further propose that liver SFA-related DNA methylation profile may contribute more to hyperglycemia, while insulin-related methylation profile is more linked to NAFLD or NASH. Further research is needed to elucidate the molecular mechanisms behind these observations.
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  • Resultat 1-5 av 5

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