Birgit Knebel1, Sonja Hartwig1, Jutta Haas2, Stefan Lehr1, Simon Goeddeke1, Franciscus Susanto1, Lothar Bohne1, Sylvia Jacob1, Cornelia Koellmer1, Ulrike Nitzgen1, Dirk Müller-Wieland2, Jorg Kotzka3. 1. Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Duesseldorf, Aufm Hennekamp 65, Duesseldorf 40225, Germany. 2. 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. 3. 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.
Abstract
UNLABELLED: 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. CONCLUSION: 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.
UNLABELLED: 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. CONCLUSION: 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: Inês Ferreira; Rita Machado de Oliveira; Ana Sofia Carvalho; Akiko Teshima; Hans Christian Beck; Rune Matthiesen; Bruno Costa-Silva; Maria Paula Macedo Journal: J Proteome Res Date: 2022-03-09 Impact factor: 4.466
Authors: Brittany A Stork; Adam Dean; Andrea R Ortiz; Pradip Saha; Nagireddy Putluri; Maricarmen D Planas-Silva; Iqbal Mahmud; Kimal Rajapakshe; Cristian Coarfa; Stefan Knapp; Philip L Lorenzi; Bruce E Kemp; Benjamin E Turk; John W Scott; Anthony R Means; Brian York Journal: Mol Metab Date: 2022-05-11 Impact factor: 8.568