Research

Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis

Mingzhe Zhu^1,6 , Guozhen Ji² , Gang Jin^1,3,4 and Zuobiao Yuan^1,5

¹Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

²Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, PR China

³ShanghaiBio Corporation, 675 US Highway One, North Brunswick, NJ, USA

⁴Shanghai Biochip Co., Ltd and National Engineering Center for Biochip at Shanghai, Shanghai, PR China

⁵Department of Surgery, University of Iowa, Iowa City, USA

⁶Graduate School of the Chinese Academy of Sciences, Shanghai, China

author email corresponding author email

Nutrition & Metabolism 2009, 6:43doi:10.1186/1743-7075-6-43

Published:	17 October 2009

Abstract

Background

To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6) and DBA/2J (D2) inbred mice.

Methods

B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data.

Results

After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis.

Conclusion

Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.