title: Lipoprotein subclass metabolism in nonalcoholic steatohepatitis.
abstract: Nonalcoholic steatohepatitis (NASH) is associated with increased synthesis of triglycerides and cholesterol coupled with increased VLDL synthesis in the liver. In addition, increased cholesterol content in the liver associates with NASH. Here we study the association of lipoprotein subclass metabolism with NASH. To this aim, liver biopsies from 116 morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, BMI 45.1 ± 6.1 kg/m², 39 men and 77 women] were used for histological assessment. Proton NMR spectroscopy was used to measure lipid concentrations of 14 lipoprotein subclasses in native serum samples at baseline and after obesity surgery. We observed that total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with NASH [false discovery rate (FDR) < 0.1]. More specifically, total lipid and cholesterol concentration of VLDL and LDL subclasses associated with inflammation, fibrosis, and cell injury (FDR < 0.1), independent of steatosis. Cholesterol concentration of all VLDL subclasses also correlated with total and free cholesterol content in the liver. All NASH-related changes in lipoprotein subclasses were reversed by obesity surgery. High total lipid and cholesterol concentration of serum VLDL and LDL subclasses are linked to cholesterol accumulation in the liver and to liver cell injury in NASH.
authors.affiliation: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Ville T
authors.initials: VT
authors.lastname: Männistö
authors.affiliation: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Simonen
authors.affiliation: NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Tiainen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kaminska
authors.affiliation: Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Venesmaa
authors.affiliation: Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Käkelä
authors.affiliation: Department of Pathology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kärjä
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
authors.affiliation: NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland Department of Medicine, Oulu University Hospital, Oulu, Finland Computational Medicine, School of Social and Community Medicine and the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.affiliation: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland Clinical Nutrition and Obesity Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000097:blood / Q000378:metabolism; D005260:Female; D005387:Finland; D015390:Gastric Bypass; D006785:Hospitals, University; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology / Q000517:prevention & control; D008055:Lipids / Q000032:analysis / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009767:Obesity, Morbid / Q000503:physiopathology* / Q000601:surgery
chemical_list: D015243:Cholesterol, VLDL; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol
keywords: high density lipoprotein; lipids; lipoproteins/metabolism; liver; low density lipoprotein; nuclear magnetic resonance; obesity; obesity surgery; very low density lipoprotein