title: Differential expression of intermediate filaments in the process of developing hepatic steatosis.
abstract: Obesity causes changes in fatty acid metabolism that consequently leads to fatty liver. To identify the possible proteins involved in the processes of obesity, we performed a proteomic analysis of obesity-induced mouse liver. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 24 wk, developed hepatic steatosis characterized by considerable increase in free fatty acid (FFA) and triglyceride levels. Body weights were measured weekly and other measurements at weeks 2, 6, 12, 16, and 24. 2-D-based proteomic analysis revealed that, compared with the normal diet (ND) (n=50), high-fat diet (n=50) changed the expression of 12 protein (8 up and 4 downregulated, by a 1.5× fold change and more, p<0.05). The most pronounced difference was observed in intermediate microfilament (IF) cytoskeleton proteins. In particular, vimentin (vim) as well as cytokeratins (CK-8 and CK-18) were significantly upregulated in obese animals. Moreover, the level of caspase-generated IF fragment was also positively correlated with the degree of steatosis. The results suggest a significant alteration in IF organization during the development of hepatic steatosis leading to inflammation. The expression profile of selected proteins including vim was validated by Western blot, microarray analysis, and hepatocyte morphology by immunohistochemistry. Our results suggest that vim, like CK-18, may be a useful marker for predicting obesity and liver disease.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Hyun Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Sujin
authors.initials: S
authors.lastname: Lee
authors.forename: Ye-Suk
authors.initials: YS
authors.lastname: Lee
authors.forename: Ung-Kyu
authors.initials: UK
authors.lastname: Choi
authors.forename: Jeong Han
authors.initials: JH
authors.lastname: Kang
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.forename: Oh-Shin
authors.initials: OS
authors.lastname: Kwon
mesh_terms: D000818:Animals; D004032:Diet; D004041:Dietary Fats; D005234:Fatty Liver / Q000378:metabolism* / Q000503:physiopathology; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism*; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009765:Obesity / Q000503:physiopathology*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D011897:Random Allocation; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D020543:Proteome; D014746:Vimentin; D007633:Keratins