Forschung & Innovation
Publikationen
Clinical and Metabolic Characterization of Lean Caucasian Subjects With Non-alcoholic Fatty Liver
PMU Autor*innen
Alexandra Feldman, Sebastian Eder, Thomas Felder, Lyudmyla Kedenko, Bernhard Paulweber, Ursula Huber-Schönauer, David Niederseer, Simon Auer, Elisabeth Haschke-Becher, Wolfgang Patsch, Elmar Aigner
Alle Autor*innen
Alexandra Feldman, Sebastian Eder, Thomas Felder, Lyudmyla Kedenko, Bernhard Paulweber, Andreas Stadlmayr, Ursula Huber-Schönauer, David Niederseer, Felix Stickel, Simon Auer, Elisabeth Haschke-Becher, Wolfgang Patsch, Christian Datz, Elmar Aigner
Fachzeitschrift
AMERICAN JOURNAL OF GASTROENTEROLOGY
Kurzfassung
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.
Keywords
Humans, Male, Aged, Middle Aged, Female, Insulin/metabolism, Alleles, GENOTYPE, ADULT, Insulin resistance, METABOLOMICS, Body Mass Index, Case-Control Studies, Adiponectin/metabolism, Glucose Intolerance/epidemiology, Lipase/genetics, Liver/diagnostic imaging, Lysine/metabolism, Lysophosphatidylcholines/metabolism, Membrane Proteins/genetics, Non-alcoholic Fatty Liver Disease/complications, Obesity/complications, Phosphatidylcholines/metabolism, Polymorphism, Single Nucleotide, Tyrosine/metabolism, Ultrasonography, Valine/metabolism, White People