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

Mingzhe Zhu,Peiyong Zheng,Guang Ji,Shijun Hao,Tao Liu,Lili Yang,Li Zhang

doi:10.18632/oncotarget.19734

Mingzhe Zhu, Peiyong Zheng + Show 5 more

Open Access

https://doi.org/10.18632/oncotarget.19734

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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.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases around the world, which is characterized by accumulation of fat deposits in the liver resulting from causes other than alcohol abuse [1, 2]
HFD feeding induced steatosis, which is the typical characteristic of non-alcoholic fatty liver disease (NAFLD) in liver sections as demonstrated by hematoxylin and eosin (H&E) staining and Oil Red O staining (Figure 1I), significantly increased hepatic TG (Figure 1H) in NAFLD rats was consistent with the histological alteration
In the present study, applying RNA-seq analysis, we observed that Lingguizhugan decoction could improve the phenotypic characteristics of NAFLD and alter a batch of gene expression

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases around the world, which is characterized by accumulation of fat deposits in the liver resulting from causes other than alcohol abuse [1, 2]. Prevalence of NAFLD has been increasing due to the modern sedentary and food-abundant lifestyle, which is 20-30% in western countries and 1520% in China [3, 4]. NAFLD is one of the most dangerous complications that can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatocellular carcinoma [5, 6]. Accumulating evidence indicates that the risks of NAFLD extend beyond the liver and are associated with a range of chronic diseases such as cardiovascular disease, chronic kidney disease and type 2 diabetes mellitus [7, 8]. Prevalence of NAFLD increases with age and is more common among males aged 45-65 years. It is spreading rapidly among children along with obesity epidemics [9]. NAFLD has become a major global health problem and brought heavy burden to patients and society

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