LC/MS-Based Untargeted Metabolomics Study in Women with Nonalcoholic Steatohepatitis Associated with Morbid Obesity

Abstract

This study investigated the importance of a metabolomic analysis in a complex disease such as nonalcoholic steatohepatitis (NASH) associated with obesity. Using an untargeted metabolomics technique, we studied blood metabolites in 216 morbidly obese women with liver histological diagnosis. A total of 172 patients were diagnosed with nonalcoholic fatty liver disease (NAFLD), and 44 were diagnosed with normal liver (NL). Patients with NAFLD were classified into simple steatosis (n = 66) and NASH (n = 106) categories. A comparative analysis of metabolites levels between NASH and NL demonstrated significant differences in lipid metabolites and derivatives, mainly from the phospholipid group. In NASH, there were increased levels of several phosphatidylinositols and phosphatidylethanolamines, as well as isolated metabolites such as diacylglycerol 34:1, lyso-phosphatidylethanolamine 20:3 and sphingomyelin 38:1. By contrast, there were decreased levels of acylcarnitines, sphingomyelins and linoleic acid. These findings may facilitate identification studies of the main pathogenic metabolic pathways related to NASH and may also have a possible applicability in a panel of metabolites to be used as biomarkers in future algorithms of the disease diagnosis and its follow-up. Further confirmatory studies in groups with different ages and sexes are necessary.

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

“…Lipidomic analysis showed that serum free fatty acids, TG, ceramides, and bile acid levels were significantly elevated in patients with MAFLD, and hepatic saturated fatty acids and poly-unsaturated fatty acid levels were also significantly higher than those in healthy people [79]. Serum acylcarnitines, sphingolipids, monoglycerides, linoleic acid, and some phosphatidylcholine levels were decreased, while diglycerides, other phosphatidylcholines, phosphatidylinositol, and phosphatidylethanolamine levels were increased in female patients with obesity and MAFLD [80]. In another study, the relative levels of serum diglycerides, TG, phosphatidylinositol, and dihydroceramides were significantly increased in patients with MAFLD, whereas the levels of phosphatidylglycerol, phosphatidylcholine, phosphatidylserine, lysophosphatidylcholine, and cholesteryl esters were decreased [81].…”