New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease

Int J Mol Sci. 2022 Jul 4;23(13):7442. doi: 10.3390/ijms23137442.

Abstract

Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic development and in some pathological processes. Although OLFM2 is involved in the regulation of the energy metabolism and OLFM4 is an important player in inflammation, innate immunity and cancer, the role of OLFMs in NAFLD-related intestinal dysbiosis remains unknown. In this study, we analysed the hepatic mRNA expression of OLFM2 and the jejunal expression of OLFM4 in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (n = 27), simple steatosis (n = 26) and nonalcoholic steatohepatitis (NASH, n = 16). Our results showed that OLFM2 hepatic mRNA was higher in NASH, in advanced degrees of steatosis and in the presence of lobular inflammation. Additionally, we obtained positive correlations between hepatic OLFM2 and glucose, cholesterol, trimethylamine N-oxide and deoxycholic acid levels and hepatic fatty acid synthase, and negative associations with weight and jejunal Toll-like receptors (TLR4) and TLR5 expression. Regarding jejunal OLFM4, we observed positive correlations with circulating interleukin (IL)-8, IL-10, IL-17 and jejunal TLR9. In conclusion, OLFM2 in the liver seems to play a relevant role in NAFLD progression, while OLFM4 in the jejunum could be involved in gut dysbiosis-related inflammatory events.

Keywords: gut-liver axis; nonalcoholic fatty liver disease; obesity; olfactomedin.

MeSH terms

  • Dysbiosis / pathology
  • Extracellular Matrix Proteins* / metabolism
  • Female
  • Glycoproteins* / metabolism
  • Granulocyte Colony-Stimulating Factor* / metabolism
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Liver / metabolism
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • RNA, Messenger / metabolism

Substances

  • Extracellular Matrix Proteins
  • Glycoproteins
  • OLFM4 protein, human
  • Olfm2 protein, human
  • RNA, Messenger
  • Granulocyte Colony-Stimulating Factor

Grants and funding

This study was funded by funds from Agència de Gestió d’Ajuts Universitaris de Recerca (AGAUR 2017 SGR 357 to Cristóbal Richart), the Grup de Recerca en Medicina Aplicada URV (2016 PFR-URV-B2-72 to Cristóbal Richart), the Investigador actiu Program from the URV (2021-10-837-AUGUET to Teresa Auguet) and own financing.