ABSTRACT
BACKGROUND: The genetic architecture of obesity is multifactorial. We have previously identified a quantitative trait locus (QTL) on rat chromosome 10 in a F2 cross of Wistar Ottawa Karlsburg (WOKW) and Dark Agouti (DA) rats responsible for obesity-related traits. The QTL was confirmed in congenic DA.WOKW10 rats. To pinpoint the region carrying causal genes, we established two new subcongenic lines, L1 and L2, with smaller refined segments of chromosome 10 to identify novel candidate genes. METHODS: All lines were extensively characterized under different diet conditions. We employed transcriptome analysis in visceral adipose tissue (VAT) by RNA-Seq technology to identify potential underlying genes in the segregating regions. Three candidate genes were measured in human paired samples of VAT and subcutaneous (SC) AT (SAT) (N=304) individuals with a wide range of body weight and glucose homeostasis parameters. RESULTS: DA.WOKW and L1 subcongenic lines were protected against body fat gain under high-fat diet (HFD), whereas L2 and DA had significantly more body fat after high-fat feeding. Interestingly, adipocyte size distribution in SAT and epigonadal AT of L1 subcongenic rats did not undergo typical ballooning under HFD and the number of preadipocytes in AT was significantly elevated in L2 compared with L1 and parental rats. Transcriptome analysis identified three candidate genes in VAT on rat chromosome 10. In humans, these candidate genes were differentially expressed between SAT and VAT. Moreover, HID1 mRNA significantly correlates with parameters of obesity and glucose metabolism. CONCLUSIONS: Our data suggest novel candidate genes for obesity that map on rat chromosome 10 in an interval 102.2-104.7 Mb and are strongly associated with body fat mass regulation, preadipocyte number and adipocyte size in rats. Among those genes, AT head involution defective (HID1) mRNA expression may be relevant for human fat distribution and glucose homeostasis.
Subject(s)
Adipocytes/metabolism , Adipocytes/pathology , Adipose Tissue/pathology , Chromosomes, Mammalian/genetics , Obesity/metabolism , Stem Cells/pathology , Animals , Cell Count , Cell Size , Disease Models, Animal , Female , Gene Expression Profiling , Genetic Techniques , Humans , Intercellular Signaling Peptides and Proteins , Male , Membrane Proteins , Mice , Mice, Inbred C57BL , Obesity/genetics , Obesity/pathology , Quantitative Trait Loci , Rats , Rats, Wistar , Real-Time Polymerase Chain ReactionABSTRACT
INTRODUCTION: Acute-on-chronic liver failure (ACLF) is a systemic inflammatory reaction, which is characterized by a predominantly proinflammatory cytokine profile, causing the transition from stable cirrhosis to ACLF. The aim of the present study was to evaluate the changes in several cytokines associated with inflammatory liver disease and liver regeneration among 15 ACLF patients treated with the Molecular Adsorbent Recirculating System (MARS) compared with 15 patients treated with standard medical therapy (SMT). The subjects showed various disease etiologies but similar values for Model End-stage Liver Disease scores. METHODS: In the MARS group, 15 (10 male and 5 female) patients were treated with MARS (Gambro). The number of MARS applications was nine; the length of applications was 8 hours. In the SMT group; 15 (10 male and 5 female) patients were treated with SMT. The patients were monitored for 30 days from inclusion with a survival follow-up at 3 months. Statistical results were calculated with SPSS14.0 (SPSS Inc, Chicago, Ill). A P < .07 was considered significant. RESULTS: In the MARS group, we observed significant changes in the levels of Interleukin (IL)-6, IL-1, IL-10, and tumor necrosis factor (TNF)-alpha in association with improved hepatocyte growth factor. Patient survival at 3 months was 60%. The SMT group showed only a significant change in TNF-alpha (P = .03). Patient survival at 3 months was 30%. CONCLUSION: The MARS liver support device corrected pathophysiologies of ALF and may be used to enhance spontaneous recovery or as a bridge to transplantation.
Subject(s)
Cytokines/blood , Liver Failure/therapy , Adsorption , Adult , Female , Humans , Liver Failure/blood , Liver Failure/physiopathology , Liver Regeneration , Male , Middle AgedABSTRACT
Adsorption equilibrium of bilirubin onto polymeric resins is studied. Solutions containing albumin are used in order to simulate the behavior of systems for removal of albumin-bound substances from blood, serum or dialysis fluids. The effect of albumin pre-loading on the resin is also analysed. Results are explained by a chemically based model that accounts for binding reaction between albumin and bilirubin in the liquid phase. Thermodynamic equilibria and physical models are essential tools for designing adsorption columns aimed at detoxification treatments.
Subject(s)
Bilirubin/isolation & purification , Polystyrenes , Resins, Synthetic , Serum Albumin, Bovine/isolation & purification , Adsorption , Animals , Bilirubin/pharmacokinetics , Buffers , Cattle , Membranes, Artificial , Serum Albumin, Bovine/pharmacokinetics , Sorption Detoxification/methodsABSTRACT
Tests of iron and folate nutrition have been carried out in early pregnancy and at delivery in 63 Bantu females. Accepted normal values for serum iron, and percentage saturation of transferrin, but not for unsaturated iron-binding capacity, for non-pregnant subjects were found to apply equally well in pregnancy. Concomitant folate deficiency in early pregnancy did not render tests of iron deficiency less valid. The unsaturated iron-binding capacity, percentage saturation, and marrow iron stores in early pregnancy all showed a significant correlation with the haemoglobin value at term. Patients with normal marrow iron stores and a percentage saturation of transferrin of 20 or more at or before the 24th week are unlikely to become anaemic from iron deficiency during pregnancy.
