Lingguizhugan decoction improves non-alcoholic fatty liver disease by altering insulin resistance and lipid metabolism related genes: a whole trancriptome study by RNA-Seq

Abstract

Lingguizhugan decoction, a classic traditional Chinese medicine formula, has been used to treat non-alcoholic fatty liver disease (NAFLD), however, the underlying mechanisms remains unclear. In the present study, we compared the phenotype of the normal rats (fed with chow diet), high-fat-diet (HFD) induced NAFLD rats and Lingguizhugan decoction (LGZG, comprises four Chinese herbs: Poria, Ramulus Cinnamomi, Rhizoma Atractylodis Macrocephalae, and Radix Glycyrrhizae.) intervened rats, and detected whole genome gene expression by RNA-Seq. Our results demonstrated that LGZG decoction attenuated phenotypic characteristics of NAFLD rats. RNA-Seq data analysis revealed that gene expression profiles exerted differential patterns between different groups. 2690 (1445 up-regulated, 1245 down-regulated) genes in NAFLD versus (vs) normal group, 69 (16 up-regulated, 53 down-regulated) genes in LGZG vs NAFLD group, and 42 overlapped (12 up- regulated, 30 down-regulated) genes between NAFLDvs normal group and LGZG vs NAFLD group were identified as differentially expressed. GO, pathway enrichment and PPI networks analysis of the overlapped genes revealed that LGZG decoction might attenuate NAFLD possibly by affecting insulin resistance and lipid metabolism related pathways (e.g., PI3K-Akt, AMPK). Differentially expressed genes involved in these pathways such as Pik3r1, Foxo1, Foxo3, Scd1, Col3a1 and Fn1 might be candidate targets for treating NAFLD.