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. 2023 Mar 29;13(4):496.
doi: 10.3390/metabo13040496.

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

Laia Bertran  1 , Laia Adalid  2 , Mercè Vilaró-Blay  1 , Andrea Barrientos-Riosalido  1 , Carmen Aguilar  1 , Salomé Martínez  2 , Fàtima Sabench  3 , Daniel Del Castillo  3 , José Antonio Porras  4 , Ajla Alibalic  4 , Cristóbal Richart  1 , Teresa Auguet  1   4
Affiliations

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

Laia Bertran et al. Metabolites. .

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.

Keywords: inflammation; lipogenesis; microbiota; nonalcoholic fatty liver disease; stimulator of interferon genes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Histological stains with hematoxylin and eosin and Masson’s trichrome stains of women with MO, (A) NL, subject with SS (B), and patients with NASH (C). NL samples show a physiological phenotype. SS presents fat accumulation in more than 5% of the tissue, whereas in NASH, in addition to excessive fat accumulation, inflammatory cells (dark blue) and scant perisinusoidal fibrosis are detected. ×400. Normal liver, NL; Simple steatosis; SS; nonalcoholic steatohepatitis, NASH.
Figure 2
Figure 2
Differential relative mRNA abundance of STING in liver samples from women with MO (A) classified as NL and NAFLD and (B) classified as NL, SS, and NASH. STING, stimulator of interferon genes; NL, normal liver; SS, simple steatosis; NASH, nonalcoholic steatohepatitis; A.U, arbitrary units. Mann–Whitney test was used to calculate the difference between groups considering p < 0.05 statistically significant.
Figure 3
Figure 3
Differential relative mRNA abundance of STING in liver samples from women with MO classified according to different grades of steatosis into absence, mild, moderate, and severe. STING, stimulator of interferons genes; A.U, arbitrary units. Mann–Whitney test was used to calculate the difference between groups considering p < 0.05 as statistically significant.
Figure 4
Figure 4
Spearman’s method was used in order to identify significant correlations between STING hepatic mRNA expression and (A) GGT, (B) ALP, (C) TLR9, (D) GCDCA, (E) GCA, (F) GDCA, (G) TCA, (H) TUDCA, and (I) GUDCA. STING, stimulator of interferon genes; GGT, gama-glutamyl transferase; ALP, alkaline phosphatase; TLR9, toll-like receptor 9; GCDCA, glycochenodeoxycholic acid; GCA, glycocholic acid; GDCA, glycodeoxycholic acid; TCA, taurocholic acid; TUDCA, tauroursodeoxycholic acid; GUDCA glycoursodeoxycholic acid; A.U arbitrary units. p < 0.05 was considered statistically significant. Spearman correlation coefficient (rho).
Figure 5
Figure 5
Representative images of the hepatic biopsies where the IHC analysis of STING was carried out (×400) in (A) NL, (B) SS, and (C) NASH groups. STING protein expression was identified as brown dots, being observed mainly in nonparenchymal cells.
See this image and copyright information in PMC

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