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Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease. | LitMetric

AI Article Synopsis

  • Nonalcoholic fatty liver disease (NAFLD) is a common and increasingly significant health issue, with its progression linked to changes in branched chain amino acids (BCAAs) like leucine, isoleucine, and valine.
  • This study examines how BCAA metabolomic changes correlate with transcriptomic changes as NAFLD progresses from simple steatosis to more severe forms like nonalcoholic steatohepatitis (NASH).
  • Key findings reveal significant increases in BCAA levels during the transition to NASH, alongside alterations in carnitine metabolites and downregulation of amino acid metabolism genes, indicating the liver's adaptive responses to metabolic stress.

Article Abstract

Nonalcoholic fatty liver disease (NAFLD) is a globally widespread disease of increasing clinical significance. The pathological progression of the disease from simple steatosis to nonalcoholic steatohepatitis (NASH) has been well defined, however, the contribution of altered branched chain amino acid metabolomic profiles to the progression of NAFLD is not known. The three BCAAs: leucine, isoleucine and valine are known to mediate activation of several important hepatic metabolic signaling pathways ranging from insulin signaling to glucose regulation. The purpose of this study is to profile changes in hepatic BCAA metabolite levels with transcriptomic changes in the progression of human NAFLD to discover novel mechanisms of disease progression. Metabolomic and transcriptomic data sets representing the spectrum of human NAFLD (normal, steatosis, NASH fatty, and NASH not fatty livers) were utilized for this study. During the transition from steatosis to NASH, increases in the levels of leucine (127% of normal), isoleucine (139%), and valine (147%) were observed. Carnitine metabolites also exhibited significantly elevated profiles in NASH fatty and NASH not fatty samples and included propionyl, hexanoyl, lauryl, acetyl and butyryl carnitine. Amino acid and BCAA metabolism gene sets were significantly enriched among downregulated genes during NASH. These cumulative alterations in BCAA metabolite and amino acid metabolism gene profiles represent adaptive physiological responses to disease-induced hepatic stress in NASH patients.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329055PMC
http://dx.doi.org/10.1007/s00726-014-1894-9DOI Listing

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