title: Lack of the Lysosomal Membrane Protein, GLMP, in Mice Results in Metabolic Dysregulation in Liver.
abstract: Ablation of glycosylated lysosomal membrane protein (GLMP, formerly known as NCU-G1) has been shown to cause chronic liver injury which progresses into liver fibrosis in mice. Both lysosomal dysfunction and chronic liver injury can cause metabolic dysregulation. Glmp gt/gt mice (formerly known as Ncu-g1gt/gt mice) were studied between 3 weeks and 9 months of age. Body weight gain and feed efficiency of Glmp gt/gt mice were comparable to wild type siblings, only at the age of 9 months the Glmp gt/gt siblings had significantly reduced body weight. Reduced size of epididymal fat pads was accompanied by hepatosplenomegaly in Glmp gt/gt mice. Blood analysis revealed reduced levels of blood glucose, circulating triacylglycerol and non-esterified fatty acids in Glmp gt/gt mice. Increased flux of glucose, increased de novo lipogenesis and lipid accumulation were detected in Glmp gt/gt primary hepatocytes, as well as elevated triacylglycerol levels in Glmp gt/gt liver homogenates, compared to hepatocytes and liver from wild type mice. Gene expression analysis showed an increased expression of genes involved in fatty acid uptake and lipogenesis in Glmp gt/gt liver compared to wild type. Our findings are in agreement with the metabolic alterations observed in other mouse models lacking lysosomal proteins, and with alterations characteristic for advanced chronic liver injury.
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway.
authors.forename: Xiang Yi
authors.initials: XY
authors.lastname: Kong
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: Eili Tranheim
authors.initials: ET
authors.lastname: Kase
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway.
authors.forename: Anette
authors.initials: A
authors.lastname: Herskedal
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Schjalm
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-Universität Kiel, Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Damme
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway.
authors.forename: Cecilie Kasi
authors.initials: CK
authors.lastname: Nesset
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway; Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors.forename: G Hege
authors.initials: GH
authors.lastname: Thoresen
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: Arild C
authors.initials: AC
authors.lastname: Rustan
authors.affiliation: Department of Bioscience, University of Oslo, Oslo, Norway.
authors.forename: Winnie
authors.initials: W
authors.lastname: Eskild
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004822:Epididymis / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D015870:Gene Expression; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006529:Hepatomegaly / Q000097:blood / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D050155:Lipogenesis / Q000235:genetics*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013163:Splenomegaly / Q000097:blood / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000235:genetics
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D051273:Glucose Transporter Type 2; D008565:Membrane Proteins; C543310:NCU-G1 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases