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

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.

• Authors: Alexandra Feldman, Sebastian K Eder, Thomas K 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
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 112 Issue 1 Pg. 102-110 (01 2017) ISSN: 1572-0241 [Electronic] United States
• PMID: 27527746 (Publication Type: Journal Article)

Chemical References

• ADIPOQ protein, human
• Adiponectin
• Insulin
• Lysophosphatidylcholines
• Membrane Proteins
• Phosphatidylcholines
• Tyrosine
• Lipase
• adiponutrin, human
• Valine
• Lysine

Topics

• Adiponectin (metabolism)
• Adult
• Aged
• Alleles
• Body Mass Index
• Case-Control Studies
• Female
• Genotype
• Glucose Intolerance (epidemiology, metabolism)
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Lipase (genetics)
• Liver (diagnostic imaging, metabolism)
• Lysine (metabolism)
• Lysophosphatidylcholines (metabolism)
• Male
• Membrane Proteins (genetics)
• Metabolomics
• Middle Aged
• Non-alcoholic Fatty Liver Disease (complications, diagnostic imaging, epidemiology, metabolism)
• Obesity (complications, metabolism)
• Phosphatidylcholines (metabolism)
• Polymorphism, Single Nucleotide
• Tyrosine (metabolism)
• Ultrasonography
• Valine (metabolism)
• White People