Biomol Ther  
Integrative Omics Reveals Metabolic and Transcriptomic Alteration of Nonalcoholic Fatty Liver Disease in Catalase Knockout Mice
Jinhyuk Na1,†, Soo An Choi1,†, Adnan Khan1, Joo Young Huh2, Lingjuan Piao3, Inah Hwang3, Hunjoo Ha3,* and Youngja H Park1,*
1College of Pharmacy, Korea University, Sejong 30019,
2College of Pharmacy, Chonnam National University, Gwangju 61186,
3Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea
E-mail: yjhwang@korea.ac.kr (Park YH), hha@ewha.ac.kr (Ha H)
Tel: +82-44-860-1621 (Park YH), +82-2-3277-4075 (Ha H)
Fax: +82-44-860-1606 (Park YH), +82-2-3277-2851 (Ha H)
The first two authors contributed equally to this work.
Received: September 10, 2018; Revised: November 18, 2018; Accepted: December 17, 2018; Published online: January 11, 2019.
© The Korean Society of Applied Pharmacology. All rights reserved.

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.
Keywords: Catalase, Nonalcoholic fatty liver disease, Liver metabolism, Inflammation, Metabolomics, Transcriptomics


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