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Journal of Lipid Research, Vol. 45, 1148-1154, June 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19

Marleen M. J. van Greevenbroek¹, Vicky M. M-J. Vermeulen and Tjerk W. A. de Bruin

Laboratory of Molecular Metabolism and Endocrinology, Cardiovascular Research Institute Maastricht (Carim), and Department of Internal Medicine, Maastricht University, UNS 50/Box 14, P.O. Box 616, 6200 MD Maastricht, The Netherlands

¹ To whom correspondence should be addressed. e-mail: m.vangreevenbroek{at}intmed.unimaas.nl

The inbred HcB19 mouse strain expresses a truncated form of thioredoxin interacting protein 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. The aim of the present study was identification of hepatic proteins specifically associated with the presence of fatty liver. 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 secretory. Four differential proteins were novel in the fatty liver proteome [i.e., aconitase, succinate dehydrogenase, propionyl CoA carboxylase 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).

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.

Abbreviations: 3HAAO, 3-hydroxyanthranilate 3,4 dioxygenase; ACO2, aconitase; ALB, albumin; ATP5B, ATP synthase ß chain; ATP5H, ATP synthase D chain; BiP, binding protein; CAT, catalase; CPS1, carbamoyl-phosphate synthase 1; ER, endoplasmic reticulum; FCHL, familial combined hyperlipidemia; FTCD, formiminotransferase cyclodeaminase; HPCL2, 2 hydroxy phytanol CoA lyase; HSPA9, heat shock protein 70 kDa protein 9; HSPA5, glucose-regulated 78 kDa protein; IEF, isoelectric focusing; MALDI-TOF, matrix-assisted laser desorption/ionization-time of flight; MW, molecular weights; NASH, nonalcoholic steatohepatitis; PCCA, propionyl CoA carboxylase chain; PRDX, peroxiredoxin; SDHA, succinate dehydrogenase subunit A; TCA, trichloroacetic acid; TF, transferrin; TG, triglyceride; TRX, thioredoxin; TXNIP, thioredoxin interacting protein

Supplementary key words 3-hydroxyanthranilate 3,4 dioxygenase • propionyl CoA carboxylase chain • proteomics • steatosis • thioredoxin • thioredoxin interacting protein

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