A distinct profile of Lyso-Phosphatidylcholines and amino acids characterizes NAFLD in lean subjects

A Feldman; SK Eder; TK Felder; A Stadlmayr; C Datz; E Aigner

doi:10.1055/s-0035-1551758

Zeitschrift für Gastroenterologie, Table of Contents

A distinct profile of Lyso-Phosphatidylcholines and amino acids characterizes NAFLD in lean subjects

A Feldman ¹, SK Eder ¹, TK Felder ², A Stadlmayr ³, C Datz ³, E Aigner ¹

¹First Department of Medicine, Paracelsus Medical University, Salzburg, Austria
²Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
³Department of Internal Medicine, General Hospital, Oberndorf, Austria

Abstract

Nonalcoholic fatty liver disease (NAFLD) is typically associated with obesity, however, approximately 10% of lean subjects also have NAFLD. The aim of this study was to identify clinical and metabolic features of NAFLD in lean Caucasian subjects.

Data from 247 patients allocated to one of 4 groups according to BMI and hepatic steatosis on ultrasound were obtained: lean healthy (BMI ≤25 kg/m², N = 76), lean steatosis (BMI ≤25 kg/m², N = 57), obese healthy (BMI ≥30 kg/m², N = 52), obese steatosis (BMI ≥30 kg/m², N = 62). A clinical and laboratory examination including oral glucose tolerance test (oGTT) was performed. Metabolite profile was obtained by API 4000 triple quadrupole mass spectrometer (ABSciex) using the AbsoluteIDQ™ p180 kit (BIOCRATES Life Sciences). Significant differences between groups were calculated using the false discovery rate (FDR) for metablomics analyses and ANOVA for comparison of clinical characteristics.

Lean NAFLD subjects had HOMA-IR similar to lean healthy subjects. However, lean NAFLD subjects had markedly impaired glucose tolerance as assessed by oGTT similar to obese NAFLD patients and significantly different from lean healthy subjects (P < 0.001). In the metabolomics analysis lower levels of sphingomyelin (OH) C14: 1, lysophosphatidylcholine (lysoPC) C18: 0, lysoPC C17: 0 (FDR < 0.001) were found in lean NAFLD compared to lean healthy subjects. A sum of lysoPC C18: 0 and C17: 0 can separate lean healthy from lean NAFLD with a ROC area under the curve (AUC) of 0.76. Additionally, in lean NAFLD subjects higher levels of PC ae C 42: 3 and lysine and lower levels of alanine, tyrosine and butyrylcarnitine (FDR < 0.001) were found when compared to obese NAFLD. ROC analysis of lysine, alanine and tyrosine discriminated lean and obese NAFLD subjects with an AUC of 0.88.

A distinct profile of lysoPCs and amino acids may be distinguishing indicators of the metabolic alterations linked to NAFLD in lean subjects.