Submitted on February 17, 2004
Revised on April 1, 2004
Accepted on March 11, 2004
Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19
M. M.J. van Greevenbroek, Vicky M.M-J Vermeulen, and Tjerk W.A. de Bruin
Internal Medicine, Maastricht University, Maastricht 6200 MD
Corresponding Author: m.vangreevenbroek{at}intmed.unimaas.nl
Introduction: The inbred HcB19 mouse strain expresses a truncated form of thioredoxin interacting protein (TXNIP) and is phenotypically characterized by fatty liver and elevated plasma triglycerides and VLDL. Recently, these mice have been proposed as an animal model for familial combined hyperlipidemia (FCHL). Aim: Identification of hepatic proteins specifically associated with the presence of fatty liver. Results: Eighteen differential proteins were detected in whole liver homogenate from HcB19 or the parental strain C3H, using 2D electrophoresis, and 11 of those were successfully identified by mass spectrometry. Five of the identified differential proteins were mitochondrial, two peroxisomal, two cytosolic and two were secretory proteins. Four differential proteins were novel in the fatty liver proteome (i.e. aconitase, ACO2; succinate dehydrogenase, SDHA; propionyl CoA carboxylase a chain, PCCA; and 3-hydroxyanthranilate 3,4 dioxygenase, 3HAAO). Of these, PCCA and 3HAAO are of particular interest because of their known functions in nicotinic acid metabolism (3HAAO) and ketogenesis (PCCA). Conclusion: We have newly identified several differential proteins in the hepatic proteome of mice with fatty liver, including PCCA and 3HAAO, and confirmed differential expression of previously reported proteins. These individual proteins, PCCA and 3HAAO, can be important in development of fatty liver or in the expression of hyperlipidemia.
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