title: Peroxisomes compensate hepatic lipid overflow in mice with fatty liver.
abstract: Major causes of lipid accumulation in liver are increased import or synthesis or decreased catabolism of fatty acids. The latter is caused by dysfunction of cellular organelles controlling energy homeostasis, i.e., mitochondria. Peroxisomes also appear to be an important organelle in lipid metabolism of hepatocytes, but little is known about their role in the development of non-alcoholic fatty liver disease (NAFLD). To investigate the role of peroxisomes alongside mitochondria in excessive hepatic lipid accumulation, we used leptin-resistant db/db mice on C57BLKS background, a mouse model that develops hyperphagia-induced diabetes with obesity and NAFLD. Proteome and gene expression analyses along with lipid analyses in the liver revealed differential expression of genes related to lipid metabolism and β-oxidation, whereas genes for peroxisomal proteins were predominantly regulated.
  
  
  CONCLUSIONS
  Our investigations show that in fatty liver disease in combination with obesity and diabetes, the hepatocyte-protecting organelle peroxisome is altered. Hence, peroxisomes might indicate a stage of pre-NAFLD, play a role in the early development of NAFLD and appear to be a potential target for treatment and prevention of NAFLD.
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Birgit
authors: B
authors: Knebel
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Sonja
authors: S
authors: Hartwig
authors: Institute for Diabetes Research, Department of General Internal Medicine, Asklepios Clinic St. Georg, Medical Faculty of Semmelweis University, Asklepios Campus Hamburg, Lohmuehlen Str 5, Hamburg 20099, Germany.
authors: Jutta
authors: J
authors: Haas
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Stefan
authors: S
authors: Lehr
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Simon
authors: S
authors: Goeddeke
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Franciscus
authors: F
authors: Susanto
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Lothar
authors: L
authors: Bohne
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Sylvia
authors: S
authors: Jacob
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Cornelia
authors: C
authors: Koellmer
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany.
authors: Ulrike
authors: U
authors: Nitzgen
authors: Institute for Diabetes Research, Department of General Internal Medicine, Asklepios Clinic St. Georg, Medical Faculty of Semmelweis University, Asklepios Campus Hamburg, Lohmuehlen Str 5, Hamburg 20099, Germany.
authors: Dirk
authors: D
authors: Müller-Wieland
authors: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany. Electronic address: jkotzka@ddz.uni-duesseldorf.de.
authors: Jorg
authors: J
authors: Kotzka
mesh_terms: D000818:Animals; D015870:Gene Expression; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020675:Peroxisomes / Q000378:metabolism / Q000502:physiology*
chemical_list: D024101:Mitochondrial Proteins
keywords: Cytokines; Dyslipidemia; Fatty acids; Gene expression; Mitochondrial and peroxisomal protein profiles; NAFLD