Nonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides.
Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH).
Dr José Mato and colleagues from Spain investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis.
The researchers collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine and spontaneously develop steatohepatitis, as well as C57Bl/6 mice.
The team determined the metabolomes of all samples.
|A serum metabolomic signature was present in 49% of the patients|
The research team also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD, and compared them with serum metabolomes of mice.
Methionine adenosyltransferase 1a knockout mice were also given hepatic S-adenosylmethionine.
The team found that livers of methionine adenosyltransferase 1a knockout mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of hepatic S-adenosylmethionine and downstream metabolites.
The research team observed a correlation between liver and serum metabolomes.
The team identified a serum metabolomic signature associated with methionine adenosyltransferase 1a knockout mice that also was present in 49% of the patients.
Based on this signature, the team identified 2 NAFLD subtypes.
The researchers identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD.
Administration of S-adenosylmethionine reduced features of steatohepatitis in methionine adenosyltransferase 1a knockout mice.
Dr Mato's team comments, "In an analysis of serum metabolomes of patients with NAFLD and methionine adenosyltransferase 1a knockout mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype."
"These might be used to monitor disease progression and identify therapeutic targets for patients."