Metabolomics Reveals Dysregulated Sphingolipid and Amino Acid Metabolism Associated with Chronic Obstructive Pulmonary Disease

Abstract

Jeeyoung Kim,1 Bharathi Suresh,2 Myoung Nam Lim,1 Seok-Ho Hong,3 Kye-Seong Kim,2,4 Ha Eun Song,5 Hyo Yeong Lee,5 Hyun Ju Yoo,5 Woo Jin Kim1 1Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea; 2Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; 3Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, South Korea; 4College of Medicine, Hanyang University, Seoul, South Korea; 5Department of Convergence Medicine, Asan Medical Center, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, South KoreaCorrespondence: Hyun Ju Yoo, Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea, Tel [phone], Fax [phone], Email [email protected] Woo Jin Kim, Department of Internal Medicine, Kangwon National University School of Medicine, 1 Gangwondaehak-gil, Chuncheon, 24341, Korea, Tel [phone], Fax [phone], Email [email protected]: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease presenting as multiple phenotypes, such as declining lung function, emphysema, or persistent airflow limitation caused by several risk factors, including cigarette smoking and air pollution. The inherent complexity of COPD phenotypes propounds difficulties for accurate diagnosis and prognosis. Although metabolomic profiles on COPD have been reported, the role of metabolism in COPD-related phenotypes is yet to be determined. In this study, we investigated the association between plasma sphingolipids and amino acids, and between COPD and COPD-related phenotypes in a Korean cohort.Patients and Methods: Blood samples were collected from 120 patients with COPD and 80 control participants who underwent spirometry and quantitative computed tomography. The plasma metabolic profiling was carried out using LC-MS/MS analysis.Results: Among the evaluated plasma sphingolipids, an increase in the metabolism of two specific sphingomyelins, SM (d18:1/24:0) and SM (d18:1/24:1) were significantly associated with COPD. There was no significant correlation between any of the SMs and the emphysema index, FVC and FEV1 in the COPD cohort. Meanwhile, Cer (d18:1/18:0) and Cer (d18:1/24:1) were significantly associated with reduced FEV1. Furthermore, the levels of several amino acids were altered in the COPD group compared to that in the non-COPD group; glutamate and alpha AAA were substantial associated with emphysema in COPD. Kynurenine was the only amino acid significantly associated with reduced FEV1 in COPD. In contrast, there was no correlation between FVC and the elevated metabolites.Conclusion: Our results provide dysregulated plasma metabolites impacting COPD phenotypes, although more studies are needed to explore the underlying mechanism related to COPD pathogenesis.Keywords: targeted sphingolipids, amino acids, sub-phenotypes, lung function

Keywords

• targeted sphingolipids
• amino acids
• sub-phenotypes
• lung function