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Alteration of Liver Peroxisomal and Mitochondrial Functionality in the NZO Mouse Model of Metabolic Syndrome
Author(s) -
Knebel Birgit,
Göddeke Simon,
Hartwig Sonja,
Hörbelt Tina,
Fahlbusch Pia,
AlHasani Hadi,
Jacob Sylvia,
Koellmer Cornelia,
Nitzgen Ulrike,
Schiller Martina,
Lehr Stefan,
Kotzka Jorg
Publication year - 2018
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201700028
Subject(s) - metabolic syndrome , peroxisome , dyslipidemia , lipidomics , insulin resistance , fatty liver , lipid metabolism , biology , medicine , mitochondrion , endocrinology , organelle , biochemistry , obesity , receptor , disease
Purpose Metabolic syndrome (MetS) consists of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia, and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation on MetS is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i.e., mitochondria and peroxisomes. Experimental design The New Zealand Obese (NZO) mouse model exhibits a polygenic syndrome of obesity, insulin resistance, triglyceridemia, and hypercholesterolemia that resembles human metabolic syndrome. We applied a multi‐omics approach combining lipidomics with liver transcriptomics and top‐down MS based organelle proteomics (2D‐DIGE) of highly enriched mitochondria and peroxisomes in male mice, to investigate molecular mechanisms related to the impact of lipid metabolism in the pathophysiology of the metabolic syndrome. Conclusions and clinical relevance Proteome analyses of liver organelles indicate differences in fatty acid and cholesterol metabolism, mainly influenced by PG‐C1α/PPARα and other nuclear receptor mediated pathways. These results are in accordance with altered serum lipid profiles and elevated organelle functionality. These data emphasize that metabolic syndrome is accompanied with increased mitochondria and peroxisomal activity to cope with dyslipidemia and hypercholesterinemia driven hepatic lipid overflow in developing a fatty liver.