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Sökning: WFRF:(Vendrell Joan)

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1.
  • Hernández-Alvarez, María Isabel, et al. (författare)
  • Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease
  • 2019
  • Ingår i: Cell. - Cell Press. - 0092-8674 .- 1097-4172. ; 177:4, s. 881-895.e17
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.</p>
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2.
  • Huth, Cornelia, et al. (författare)
  • IL6 gene promoter polymorphisms and type 2 diabetes - Joint analysis of individual participants' data from 21 studies
  • 2006
  • Ingår i: DIABETES. - 0012-1797. ; 55:10, s. 2915-2921
  • Tidskriftsartikel (refereegranskat)abstract
    • Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G > C (rs1800795) and -573G > C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on > 20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G > C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 -573G > C and type 2 diabetes. The observed association of the IL6 -174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.
3.
  • Huth, Cornelia, et al. (författare)
  • Joint analysis of individual participants' data from 17 studies on the association of the IL6 variant -174G>C with circulating glucose levels, interleukin-6 levels, and body mass index.
  • 2009
  • Ingår i: Annals of medicine. - 1365-2060. ; 41:2, s. 128-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Several studies have investigated associations between the -174GC single nucleotide polymorphism (rs1800795) of the IL6 gene and phenotypes related to type 2 diabetes mellitus (T2DM) but presented inconsistent results. Aims. This joint analysis aimed to clarify whether IL6 -174GC was associated with glucose and circulating interleukin-6 concentrations as well as body mass index (BMI). Methods. Individual-level data from all studies of the IL6-T2DM consortium on Caucasian subjects with available BMI were collected. As study-specific estimates did not show heterogeneity (P0.1), they were combined by using the inverse-variance fixed-effect model. Results. The main analysis included 9440, 7398, 24,117, or 5659 non-diabetic and manifest T2DM subjects for fasting glucose, 2-hour glucose, BMI, or circulating interleukin-6 levels, respectively. IL6 -174 C-allele carriers had significantly lower fasting glucose (-0.091 mmol/L, P=0.014). There was no evidence for association between IL6 -174GC and BMI or interleukin-6 levels, except in some subgroups. Conclusions. Our data suggest that C-allele carriers of the IL6 -174GC polymorphism have lower fasting glucose levels on average, which substantiates previous findings of decreased T2DM risk of these subjects.
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