Clinical and Metabolic Characterization of Lean Caucasian... : Official journal of the American College of Gastroenterology | ACG (original) (raw)

ORIGINAL CONTRIBUTIONS: LIVER

Clinical and Metabolic Characterization of Lean Caucasian Subjects With Non-alcoholic Fatty Liver

Feldman, Alexandra MD1,2,7; Eder, Sebastian K MD1,2,7; Felder, Thomas K PhD2,3; Kedenko, Lyudmyla MD1; Paulweber, Bernhard MD1,2; Stadlmayr, Andreas MD4; Huber-Schönauer, Ursula PhD4; Niederseer, David MD4; Stickel, Felix MD5; Auer, Simon BS3; Haschke-Becher, Elisabeth MD3; Patsch, Wolfgang MD6; Datz, Christian MD2,4,8; Aigner, Elmar MD1,2,8

1First Department of Medicine, Paracelsus Medical University, Salzburg, Austria

2Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria

3Department of Laboratory Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria

4Department of Internal Medicine, Hospital Oberndorf, Austria

5Hepatology Unit, Clinic Beau-Site, Bern and Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland

6Department of Pharmacology and Toxicology, Paracelsus Medical University Salzburg, Salzburg, Austria

Correspondence: Elmar Aigner, MD, Department of Internal Medicine, General Hospital Oberndorf, Paracelsusstrasse 37, A-5110 Oberndorf, Austria

Correspondence: Elmar Aigner, MD, First Department of Medicine, Paracelsus Private Medical University Salzburg, Mìllner Hauptstrasse 48, Salzburg 5020, Austria. E-mails: [email protected] and [email protected]

7These authors contributed equally to this work.

8These authors contributed equally to this work

SUPPLEMENTARY MATERIAL accompanies this paper at https://links.lww.com/AJG/A355

Received 08 March 2016; accepted 02 June 2016

Guarantor of the article: Christian Datz, MD.

Specific author contributions: Data analysis, drafting and writing of manuscript: A.F. and S.K.E; patient recruitment, data acquisition and revision of manuscript for important intellectual content: T.K.F., B.P., L.K., A.S., U.H.S., D.N., F.S., S.A., E.H.B., and W.P.; study concept and design, analysis and interpretation of data, outlining and revising the manuscript: C.D. and E.A.

Financial support: Elmar Aigner is supported by PMU Research Fund PMU-FFF (E-13/17/086-AIG and E-15/21/108-AIE). Support from Spar Austria to Christian Datz is gratefully acknowledged.

Potential competing interests: None.

Abstract

Objectives:

Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity; however, 5–8% of lean subjects also have evidence of NAFLD. We aimed to investigate clinical, genetic, metabolic and lifestyle characteristics in lean Caucasian subjects with NAFLD.

Methods:

Data from 187 subjects allocated to one of the three groups according to body mass index (BMI) and hepatic steatosis on ultrasound were obtained: lean healthy (BMI≤25 kg/m2, no steatosis, N =71), lean NAFLD (BMI≤25 kg/m2, steatosis, N =55), obese NAFLD (BMI≥30 kg/m2, steatosis; N =61). All subjects received a detailed clinical and laboratory examination including oral glucose tolerance test. The serum metabolome was assessed using the Metabolomics AbsoluteIDQ p180 kit (BIOCRATES Life Sciences). Genotyping for single-nucleotide polymorphisms (SNPs) associated with NAFLD was performed.

Results:

Lean NAFLD subjects had fasting insulin concentrations similar to lean healthy subjects but had markedly impaired glucose tolerance. Lean NAFLD subjects had a higher rate of the mutant PNPLA3 CG/GG variant compared to lean controls ( P =0.007). Serum adiponectin concentrations were decreased in both NAFLD groups compared to controls ( P <0.001 for both groups) The metabolomics study revealed a potential role for various lysophosphatidylcholines (lyso-PC C18:0, lyso-PC C17:0) and phosphatidylcholines (PCaa C36:3; false discovery rate (FDR)-corrected P -value<0.001) as well as lysine, tyrosine, and valine (FDR<0.001).

Conclusions:

Lean subjects with evidence of NAFLD have clinically relevant impaired glucose tolerance, low adiponectin concentrations and a distinct metabolite profile with an increased rate of PNPLA3 risk allele carriage.