The Role of Olfactomedin 2 in the Adipose Tissue–Liver Axis and Its Implication in Obesity-Associated Nonalcoholic Fatty Liver Disease

Abstract

This study’s objective was to assess the involvement of olfactomedin 2 (OLFM2), a secreted glycoprotein related to lipid metabolism regulation, in nonalcoholic fatty liver disease (NAFLD) mediated by the adipose-tissue–liver axis. OLFM2 mRNA expression was analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue by RT–qPCR. The cohort included women with normal weight (n = 16) or morbid obesity (MO, n = 60) who were subclassified into normal liver (n = 20), simple steatosis (n = 21), and nonalcoholic steatohepatitis (NASH, n = 19) groups. The results showed that OLFM2 expression in SAT was enhanced in MO individuals and in the presence of NAFLD. Specifically, OLFM2 expression in SAT was increased in mild and moderate degrees of steatosis in comparison to the absence of it. Moreover, OLFM2 expression in SAT was negatively correlated with interleukin-6 levels. On the other hand, OLFM2 expression in VAT decreased in the presence of NASH and exhibited a positive correlation with adiponectin levels. In conclusion, OLFM2 in SAT seems to be implicated in hepatic lipid accumulation. Additionally, since we previously suggested the possible implication of hepatic OLFM2 in NAFLD progression, now we propose a possible interaction between the liver and SAT, reinforcing the potential implication of this tissue in NAFLD development.

The Role of the Olfactory System in Obesity and Metabolism in Humans: A Systematic Review and Meta-Analysis

“…Odors sensed by the olfactory system change the activation status of hypothalamic AgRP Metabolites 2024, 14, 16 2 of 23 and POMC neurons, thereby modulating appetite and satiety circuits [13][14][15]. Furthermore, olfactory cues also influence thermogenesis and peripheral metabolism, possibly mediated by olfactomedin 2 (OLFM2), a protein that plays a significant role in energy balance modulation [16][17][18]. The integration of olfactory signals with hypothalamic regulation underscores a complex but crucial aspect of the energy balance, influencing feeding behavior, thermogenesis, and overall systemic metabolism.…”