Expression of STING in Women with Morbid Obesity and Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disease. Although mostly benign, this disease can evolve into nonalcoholic steatohepatitis (NASH). The stimulator of interferon genes (STING) plays an important role in the immune response against stressed cells, but this protein may also be involved in liver lipogenesis and microbiota composition. In this study, the role of STING in NAFLD was evaluated by RT–qPCR to analyze STING mRNA abundance and by immunohistochemical analysis to evaluate protein expression in liver biopsies from a cohort composed of 69 women with morbid obesity classified according to their liver involvement (normal liver, n = 27; simple steatosis (SS), n = 26; NASH, n = 16). The results showed that STING mRNA expression in the liver increases with the occurrence of NAFLD, specifically in the SS stage in which the degree of steatosis is mild or moderate. Protein analysis corroborated these results. Positive correlations were observed among hepatic STING mRNA abundance and gamma-glutamyl transferase and alkaline phosphatase levels, hepatic Toll-like receptor 9 expression and some circulating microbiota-derived bile acids. In conclusion, STING may be involved in the outcome and progression of NAFLD and may be related to hepatic lipid metabolism. However, further studies are needed to confirm these findings.

Update on the STING Signaling Pathway in Developing Nonalcoholic Fatty Liver Disease

“…Fibrosis is a critical characteristic of advanced NAFLD, and its presence may influence STING expression differently compared to earlier stages of the disease. 30 Studies have also found that the levels of cGAS and STING proteins increased in liver carcinoma patients with the increase in liver fibrosis, and were higher than in the surrounding cancer tissues. 31 These contrasting findings highlight the complexity of the STING signaling pathway’s involvement in NAFLD and the need for further research to fully understand its role in different stages of the disease.…”