Roles of Gut-Derived Secretory Factors in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Their Possible Clinical Applications

Int J Mol Sci. 2018 Oct 8;19(10):3064. doi: 10.3390/ijms19103064.

Abstract

The rising prevalence of non-alcoholic fatty liver disease (NAFLD) parallels the global increase in the number of people diagnosed with obesity and metabolic syndrome. The gut-liver axis (GLA) plays an important role in the pathogenesis of NAFLD/non-alcoholic steatohepatitis (NASH). In this review, we discuss the clinical significance and underlying mechanisms of action of gut-derived secretory factors in NAFLD/NASH, focusing on recent human studies. Several studies have identified potential causal associations between gut-derived secretory factors and NAFLD/NASH, as well as the underlying mechanisms. The effects of gut-derived hormone-associated drugs, such as glucagon-like peptide-1 analog and recombinant variant of fibroblast growth factor 19, and other new treatment strategies for NAFLD/NASH have also been reported. A growing body of evidence highlights the role of GLA in the pathogenesis of NAFLD/NASH. Larger and longitudinal studies as well as translational research are expected to provide additional insights into the role of gut-derived secretory factors in the pathogenesis of NAFLD/NASH, possibly providing novel markers and therapeutic targets in patients with NAFLD/NASH.

Keywords: fibroblast growth factor 19; glucagon-like peptide-1; glucagon-like peptide-2; gut-liver axis; neurotensin; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; resistin like molecule β.

Publication types

  • Review

MeSH terms

  • Animals
  • Enteroendocrine Cells / metabolism*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Glucagon-Like Peptides / genetics
  • Glucagon-Like Peptides / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neurotensin / genetics
  • Neurotensin / metabolism
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / therapy

Substances

  • FGF19 protein, human
  • Intercellular Signaling Peptides and Proteins
  • RETNLB protein, human
  • Neurotensin
  • Fibroblast Growth Factors
  • Glucagon-Like Peptides