title: Clinical and Metabolic Characterization of Lean Caucasian Subjects With Non-alcoholic Fatty Liver.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Feldman
authors.affiliation: First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Sebastian K
authors.initials: SK
authors.lastname: Eder
authors.affiliation: Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.|Department of Laboratory Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Felder
authors.affiliation: First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Kedenko
authors.affiliation: First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.affiliation: Department of Internal Medicine, Hospital Oberndorf, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stadlmayr
authors.affiliation: Department of Internal Medicine, Hospital Oberndorf, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Huber-Schönauer
authors.affiliation: Department of Internal Medicine, Hospital Oberndorf, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Niederseer
authors.affiliation: Hepatology Unit, Clinic Beau-Site, Bern and Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.affiliation: Department of Laboratory Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Simon
authors.initials: S
authors.lastname: Auer
authors.affiliation: Department of Laboratory Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Haschke-Becher
authors.affiliation: Department of Pharmacology and Toxicology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
authors.affiliation: Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.|Department of Internal Medicine, Hospital Oberndorf, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.affiliation: First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Elmar
authors.initials: E
authors.lastname: Aigner
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D018149:Glucose Intolerance / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008049:Lipase / Q000235:genetics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D055432:Metabolomics; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D014443:Tyrosine / Q000378:metabolism; D014463:Ultrasonography; D014633:Valine / Q000378:metabolism; D044465:White People; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D052242:Adiponectin; D007328:Insulin; D008049:Lipase; D008239:Lysine; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D014443:Tyrosine; D014633:Valine; C499918:ADIPOQ protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent