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Differential expression of intermediate filaments in the process of developing hepatic steatosis
Author(s) -
Park JungEun,
Kim Hyun Tae,
Lee Sujin,
Lee YeSuk,
Choi UngKyu,
Kang Jeong Han,
Choi Soo Young,
Kang TaeCheon,
Choi MyungSook,
Kwon OhShin
Publication year - 2011
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201000544
Subject(s) - steatosis , fatty liver , medicine , endocrinology , biology , western blot , lipogenesis , vimentin , hepatocyte , carbohydrate responsive element binding protein , desmin , immunohistochemistry , lipid metabolism , biochemistry , disease , gene , in vitro , transcription factor
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.