Ketone body production is differentially altered in steatosis and non-alcoholic steatohepatitis in obese humans

Background & AimsLevels of ketone bodies have been reported to be both increased and decreased in individuals with non-alcoholic fatty liver disease. We investigated whether the metabolism of ketone bodies is different in simple steatosis and in non-alcoholic steatohepatitis (NASH). MethodsSerum low molecular weight molecules including ketone bodies were measured using high-throughput proton (1H) nuclear magnetic resonance in 116 (76 categorized unequivocally to those with normal liver, simple steatosis or NASH) morbidly obese individuals [age 47.38.7 (meanSD) years, body mass index 45.1 +/- 6.1kg/m(2), 39 men and 77 women] with histological assessment of NASH and analysis of gene expression in the liver. Finally, we correlated -hydroxybutyrate (-OHB) levels with NASH predicting score in Metabolic Syndrome in Men Study (METSIM) population study (n=8749 non-diabetic men). ResultsLevels of ketone bodies were lower in individuals with NASH compared to individuals with simple steatosis (P=0.004 and P=0.018 for -OHB and acetoacetate respectively). Lower levels of -OHB were associated with the NASH predicting score in the METSIM study (P=0.001). Liver inflammation correlated with mRNA expression of genes regulating ketolysis in the liver (Spearman correlation 0.379-0.388, P<0.0006 for ACAT1, ACSS2 and BDH1). ConclusionLower levels of ketone bodies in individuals with NASH compared to individuals with simple steatosis suggest a decrease in ketone body metabolism in NASH.