Biomol Ther.  2019 Feb;27(2):134-144. 10.4062/biomolther.2018.175.

Integrative Omics Reveals Metabolic and Transcriptomic Alteration of Nonalcoholic Fatty Liver Disease in Catalase Knockout Mice

• Na J
• Choi SA
• Khan A
• Huh JY
• Piao L
• Hwang I
• Ha H
• Park YH

• KMID: 2442004
• DOI: http://doi.org/10.4062/biomolther.2018.175

Abstract

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and 3β, 7α-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and α/γ-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

Keyword

Catalase; Nonalcoholic fatty liver disease; Liver metabolism; Inflammation; Metabolomics; Transcriptomics

MeSH Terms

alpha-Linolenic Acid
Animals
Bile
Catalase
Cholic Acid
Diet
Diet, High-Fat
Eicosapentaenoic Acid
Fatty Liver
Gene Deletion
Incidence
Inflammation
Liver
Metabolism
Metabolomics
Mice
Mice, Knockout*
Models, Animal
Non-alcoholic Fatty Liver Disease*
Obesity
Oxidative Stress
Prevalence
Thromboxane A2
Vitamin A
Catalase
Cholic Acid
Eicosapentaenoic Acid
Thromboxane A2
Vitamin A
alpha-Linolenic Acid