title: A serum metabolomic investigation on lipoprotein lipase-deficient mice with hyperlipidemic pancreatitis using gas chromatography/mass spectrometry.
abstract: Hypertriglyceridemia (HTG) is often associated with acute pancreatitis. The relationship between these diseases and the role that hypertriglyceridemia plays in acute pancreatitis pathogenesis remains to be elucidated. In the present study, in order to investigate the mechanisms of hyper-lipidemic acute pancreatitis (HLP), we established an animal model using lipoprotein lipase (LPL)-deficient heterozygous mice injected with caerulein. Susceptibility to pancreatitis in LPL-deficient heterozygous mice was compared with that of wild-type mice after intraperitoneal (i.p.) injections of caerulein by determining amylase release and pancreatic pathological scores. Furthermore, serum metabolome was detected through chemical derivatization followed by gas chromatography/mass spectrometry (GC/MS). GC/MS data were analyzed by orthogonal-projection to latent structures-discriminant analysis (OPLS-DA). Caerulein induced increased levels of serum amylase and more severe pancreatic inflammation in LPL-deficient mice compared to wild-type mice. HLP was discriminated more accurately from healthy controls by the metabolites, including valine, leucine and citrate. The metabolites included valine, leucine, citrate, malic acid, proline, tetradecanoic acid (14:0), glutamine and oleic acid (18:1). Changes in energy, fat and amino acid metabolism were also evident. In conclusion, LPL-deficient heterozygous mice with hypertriglyceridemia (HTG) exhibited enhanced susceptibility to acute pancreatitis. GC/MS data revealed differences between healthy and HLP mice. Therefore, this technique is novel and a useful tool for the study of the HLP pathogenetic mechanism.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072;
authors.forename: Maochun
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072;
authors.forename: Gouyong
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072;
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240;
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100083;
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240;
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Shanghai Institute for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100083;
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072;
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
keywords: blood; hyperlipidemic acute pancreatitis; lipoprotein lipase; metabolism