Circulating lipidomic alterations in obese and non-obese subjects with non-alcoholic fatty liver disease

Youngae Jung, Min Kyung Lee, Puneet Puri, Bo Kyung Koo, Sae Kyung Joo, Seo Young Jang, Dong Hyeon Lee, Yong Jin Jung, Byeong Gwan Kim, Kook Lae Lee, Tae Sik Park, Ki Tae Kang, Do Hyun Ryu, Sang Won Kang, Donghee Kim, Sohee Oh, Won Kim, Geum Sook Hwang

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24 Scopus citations

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) affects obese and non-obese individuals. However, mechanisms underlying non-obese non-alcoholic steatohepatitis (NASH) remain unclear. Aims: To attempt to identify metabolic perturbations associated with non-obese and obese NAFLD using a lipidomics approach. Methods: A cross-sectional analysis of 361 subjects with biopsy-proven NAFLD (157 NAFL and 138 NASH) and healthy controls (n = 66) was performed. Individuals were categorised as obese or non-obese based on the Asian cut-off for body mass index. Circulating lipidomic profiling of sera was performed based on the histological severity of NAFLD. Circulating lipidomic alterations were validated with an independent validation set (154 NAFLD subjects [93 NAFL and 61 NASH] and 21 healthy controls). Results: Saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in non-obese NAFLD (SM d38:0; P < 0.001) but not in obese NAFLD. Additionally, SM levels were significantly associated with systemic and adipose tissue insulin resistance (SM d38:0; P = 0.002 and <0.001, respectively). Five potential lipid metabolites for non-obese subjects and seven potential lipids for obese subjects were selected to predict NAFLD and NASH. These lipid combinations showed good diagnostic performance for non-obese (area under the curve [AUC] for NAFLD/NASH = 0.916/0.813) and obese (AUC for NAFLD/NASH = 0.967/0.812) subjects. Moreover, distinctly altered patterns of diacylglycerol (DAG), triacylglycerol (TAG) and SM levels were confirmed in the validation set depending on the histological severity of NAFLD. Conclusion: Non-obese and obese NAFLD subjects exhibit unique circulating lipidomic signatures, including DAGs, TAGs and SMs. These lipid combinations may be useful biomarkers for non-obese and obese NAFLD patients.

Original languageEnglish
Pages (from-to)1603-1614
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume52
Issue number10
DOIs
StatePublished - 1 Nov 2020

Bibliographical note

Funding Information:
G‐S. Hwang was supported by the Korea Basic Science Institute (C060200) and National Research Foundation of Korea (NRF) grant funded by the Korean Government (NRF‐2017M3A9C4065961 and NRF‐2017M3A9D5A01052449). W. Kim was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MEST; 2016R1D1A1B04934590) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (H I17C0912). The funding organisation played no role in the design and conduct of the study; in the collection, management, analysis and interpretation of data; or in the preparation, review or approval of the manuscript.

Funding Information:
G-S. Hwang was supported by the Korea Basic Science Institute (C060200) and National Research Foundation of Korea (NRF) grant funded by the Korean Government (NRF-2017M3A9C4065961 and NRF-2017M3A9D5A01052449). W. Kim was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MEST; 2016R1D1A1B04934590) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (H I17C0912). The funding organisation played no role in the design and conduct of the study; in the collection, management, analysis and interpretation of data; or in the preparation, review or approval of the manuscript. Declaration of personal interests: Youngae Jung: None. Min Kyung Lee: None. Punnet Puri: None. Bo Kyung Koo: None. Sae Kyung Joo: None. See Young Jang: None. Dong Hyeon Lee: None. Yong Jin Jung : None. Byeong Gowan Kim: None. Kook Lae Lee: None. Tae-Sik Park: None. Ki-Tae Kang: None. Do Hyun Ryu: None. Sang Won Kang: None. Donghee Kim: None. Sohee Oh: None. Won Kim: has served as a speaker and consultant of Gilead, Boehringer-Ingelheim, Samil, Ildong, LG Chemistry, CJ healthcare-Kolmar, GreenCross, Bukwang, Standigm, PharmaKing, KOBIOLABS and Eisai, and owns stocks in KOBIOLABS and Lepidyne. Geum-Sook Hwang: None Declaration of funding interests: This study was supported in part by Korea Basic Science Institute (C060200), Korea Health Industry Development Institute (HI17C0912) and National Research Foundation of Korea (2016R1D1A1B04934590, NRF-2017M3A9C4065961 and NRF-20173A9D5A01052449). The funding organizations played no role in the design and conduct of the study; in the collection, management, analysis and interpretation of data; or in the preparation, review and approval of the manuscript.

Funding Information:
: This study was supported in part by Korea Basic Science Institute (C060200), Korea Health Industry Development Institute (HI17C0912) and National Research Foundation of Korea (2016R1D1A1B04934590, NRF‐2017M3A9C4065961 and NRF‐20173A9D5A01052449). The funding organizations played no role in the design and conduct of the study; in the collection, management, analysis and interpretation of data; or in the preparation, review and approval of the manuscript. Declaration of funding interests

Publisher Copyright:
© 2020 John Wiley & Sons Ltd

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