Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver

Abstract

Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote fatty liver in mice, while cis-9, trans-11-CLA ameliorates this effect, suggesting regulation of multiple genes. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid isomers, and their hepatic gene expression was analyzed with DNA microarrays. To provide an initial screening of candidate genes, only 12 with remarkably modified expression between both CLA isomers were considered and confirmed by quantitative RT-PCR. Additionally mRNA expression of 15 genes involved in lipid metabolism was also studied. Ten genes (Fsp27, Aqp4, Cd36, Ly6d, Scd1, Hsd3b5, Syt1, Cyp7b1, and Tff3) showed significant associations among their expressions and the degree of hepatic steatosis. Their involvement was also analyzed in other models of steatosis. In hyperhomocysteinemic mice lacking Cbs gene, only Fsp27, Cd36, Scd1, Syt1, and Hsd3b5 hepatic expressions were associated with steatosis. In apoE-deficient mice consuming olive-enriched diet displaying reduction of the fatty liver, only Fsp27 and Syt1 expressions were found associated. Using this strategy, we have shown that expression of these genes is highly associated with hepatic steatosis in a genetic disease such as Cbs deficiency and in two common situations such as Western diets containing CLA isomers or a Mediterranean-type diet. Conclusion: The results highlight new processes involved in lipid handling in liver and will help to understand the complex human pathology providing new proteins and new strategies to cope with hepatic steatosis.

Trefoil Factor 3 Deficiency Affects Liver Lipid Metabolism

“…The first function of Tff3 protein was connected with protection of gastrointestinal tract injuries but recent data connect Tff3 protein with metabolically relevant conditions [8,12]. The results of the present study showed that Tff3 protein deficiency affects the metabolism of fatty acids in the liver (Fig.…”

“…All of the above contributes to the complexity of this issue and additionally underlines the complexity of metabolic regulation. Nevertheless, reduced expression of liver Tff3 was noticed in different obese mice models of various genetic background (High fat induced obesity, Lepr db /Lepr db and Lepr ob /Lepr ob ) [10], early diabetic mice [8] and steatotic liver [12], connecting Tff3 deficiency with conditions caused by specific diseases. Additionally, liver Tff3 expression was most dramatic (reduction by 600x) in the early diabetes phase of multigene diabesity model called Tally Ho mice [8].…”

Cystathionine β-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites

“….). This strategy had been proved really valuable in our hands (15,16) and indicates that pooled samples of histologically comparable tissues can successfully be used to provide an initial screening of gene expression in studies of this type, with the attending economic and time savings, although with the limitation of no information on biological variability.…”

Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

“…Guillen et al (51) found several genes (Fsp27, Cd36, Scd1, Syt1, and Hsd3b5) upregulated in the livers of 9-day-old cbs Ϫ/Ϫ pups. Among these, Cd36 sensitizes endothelial cells to the antimigration and antitube formation effects of thrombospondin-1 (29).…”