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

• Published in: International journal of molecular sciences Vol. 23; no. 13; p. 7442
• Main Authors: Bertran, Laia, Jorba-Martin, Rosa, Barrientos-Riosalido, Andrea, Portillo-Carrasquer, Marta, Aguilar, Carmen, Riesco, David, Martínez, Salomé, Vives, Margarita, Sabench, Fàtima, Castillo, Daniel Del, Richart, Cristóbal, Auguet, Teresa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04-07-2022; MDPI
• Subjects: Blood pressure; Body fat; Body mass index; Cancer; Cholesterol; Deoxycholic acid; Digestive system; Dysbacteriosis; Dysbiosis - pathology; Embryogenesis; Energy metabolism; Extracellular Matrix Proteins - metabolism; Fatty liver; Fatty-acid synthase; Female; Gene expression; Glucose; Glycoproteins; Glycoproteins - metabolism; Granulocyte Colony-Stimulating Factor - metabolism; gut-liver axis; Histology; Humans; Inflammation; Inflammation - metabolism; Inflammation - pathology; Innate immunity; Interleukin 10; Interleukin 17; Jejunum; Lipids; Liver; Liver - metabolism; Liver diseases; Metabolism; Metabolites; Microbiota; Non-alcoholic Fatty Liver Disease - metabolism; nonalcoholic fatty liver disease; Obesity; olfactomedin; Pathogenesis; Permeability; Proteins; RNA, Messenger - metabolism; Small intestine; Steatosis; TLR4 protein; TLR5 protein; TLR9 protein; Toll-like receptors; Trimethylamine; Womens health; olfactomedin; nonalcoholic fatty liver disease; gut-liver axis; obesity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23137442

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
and the jejunal expression of
in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (
= 27), simple steatosis (
= 26) and nonalcoholic steatohepatitis (NASH,
= 16). Our results showed that
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
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 (
) and
expression. Regarding jejunal
, we observed positive correlations with circulating interleukin (IL)-8, IL-10, IL-17 and jejunal
. 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.