Detection of differentially expressed candidate genes for a fatty liver QTL on mouse chromosome 12. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Kobayashi, Misato; Suzuki, Miyako; Ohno, Tamio; Tsuzuki, Kana; Taguchi, Chie; Tateishi, Soushi; Kawada, Teruo; Kim, Young-il; Murai, Atsushi; Horio, Fumihiko
• Is Part Of: BMC genetics. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Genetics -- Nutrition -- Liver -- Lipids -- Fatty acids -- CD36 -- Consomic -- High-fat diet; Genetics -- Periodicals; 576.505
• DOI: 10.1186/s12863-016-0385-2
• Languages: English
• ISSNs: 1471-2156

Abstract

Abstract Background The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was identified in a SM/J × SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele ofFl1sa is a fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver withinFl1sa was confirmed in A/J-12SM consomic mice. The aim of this study was to identify candidate genes forFl1sa, and to investigate whether the identified genes affect the lipid metabolism. Results A/J-12SM mice showed a significantly lower liver triglyceride content compared to A/J mice when fed the high-fat diet for 7 weeks. We detected differences in the accumulation of liver lipids in response to the high-fat diet between A/J and A/J-12SM consomic mice. To identify candidate genes forFl1sa, we performed DNA microarray analysis using the livers of A/J-12SM and A/J mice fed the high-fat diet. The mRNA levels of three genes (Iah1, Rrm2, Prkd1 ) in the chromosomal region ofFl1sa were significantly different between the strains.Iah1 mRNA levels in the liver, kidney, and lung were significantly higher in A/J-12SM mice than in A/J mice. The hepaticIah1 mRNA level in A/J-12SM mice was 3.2-fold higher than that in A/J mice. To examine the effect ofIah1 on hepatic lipid metabolism, we constructed a stable cell line expressing the mouse Iah1 protein in mouse hepatoma Hepa1-6 cells. Overexpression of Iah1 in Hepa1-6 cells suppressed the mRNA levels ofCd36 andDgat2, which play important roles in triglyceride synthesis and lipid metabolism. Conclusions These results demonstrated thatFl1sa on the proximal region of chromosome 12 affected fatty liver in mice on a high-fat diet.Iah1 (isoamyl acetate-hydrolyzing esterase 1 homolog) was identified as one of the candidate genes forFl1sa . This study revealed that the mouseIah1 gene regulated the expression of genes related to lipid metabolism in the liver.