title: Using proteomics to discover novel biomarkers for fatty liver development and response to CB1R antagonist treatment in an obese mouse model.
abstract: Over activity of cannabinoid receptor type 1 (CB1R) plays a key role in increasing the incidence of obesity-induced non-alcoholic fatty liver disease. Tissue proteome analysis has been applied to investigate the bioinformatics regarding the mode of action and therapeutic mechanism. The aim of this study was to explore the potential pathways altered with CB1R in obesity-induced fatty liver. Male C57BL/6 mice were fed either a standard chow diet (STD) or a high-fat diet (HFD) with or without 1-week treatment of CB1R inverse agonist AM251 at 5 mg/kg. Then, liver tissues were harvested for 2DE analysis and protein profiles were identified by using MALDI-MS. Results showed that eight of significantly altered protein spots at the level of changes > twofold were overlapped among the three groups, naming major urinary protein 1, ATP synthase subunit β, glucosamine-fructose-6-phosphate aminotransferase 1, zine finger protein 2, s-adenosylmethionine synthase isoform type-1, isocitrate dehydrogenase subunit α, epoxide hydrolase 2 and 60S acidic ribosomal protein P0. These identified proteins were involved in glucose/lipid metabolic process, xenobiotic metabolic system, and ATP synthesized process in mitochondria. Based on the findings, we speculated that CB1R blockade might exert its anti-metabolic disorder effect via improvement of mitochondrial function in hepatic steatosis in HFD condition.
authors.affiliation: Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.|Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chin-Chang
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tzung-Yan
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ching-Fai
authors.initials: CF
authors.lastname: Kwok
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yung-Pei
authors.initials: YP
authors.lastname: Hsu
authors.affiliation: Department of Medicine-Metabolism, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Kuang-Chung
authors.initials: KC
authors.lastname: Shih
authors.affiliation: Department of Research Planning and Development, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.|Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D063387:Cannabinoid Receptor Antagonists / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D010880:Piperidines / Q000627:therapeutic use*; D040901:Proteomics / Q000379:methods*; D011720:Pyrazoles / Q000627:therapeutic use*; D043882:Receptors, Cannabinoid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; C103505:AM 251
keywords: Animal proteomics; Cannabinoid receptor type 1; High-fat diet; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis