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OLFM2 和 OLFM4 在肠-肝轴中的新见解及其在非酒精性脂肪性肝病中的潜在作用。

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

机构信息

Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43007 Tarragona, Spain.

Servei de Cirurgia General i de l'Aparell Digestiu, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Mallafré Guasch, 4, 43007 Tarragona, Spain.

出版信息

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 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.

摘要

嗅觉素(OLFMs)是一类糖蛋白,在胚胎发育和某些病理过程中发挥重要作用。虽然 OLFM2 参与调节能量代谢,OLFM4 是炎症、先天免疫和癌症的重要参与者,但 OLFMs 在与 NAFLD 相关的肠道菌群失调中的作用尚不清楚。在这项研究中,我们分析了患有病态肥胖(MO)的女性中一个成熟队列的肝脏 mRNA 表达和空肠表达。这些女性根据其肝组织学分为正常肝脏(=27)、单纯性脂肪变性(=26)和非酒精性脂肪性肝炎(NASH,=16)。我们的结果表明,NASH 组、脂肪变性程度较高组和存在肝小叶炎症组的肝脏中 mRNA 水平较高。此外,我们还发现肝脏与葡萄糖、胆固醇、三甲胺 N-氧化物和脱氧胆酸水平之间存在正相关,与体重和空肠 Toll 样受体(TLRs)和表达之间存在负相关。关于空肠,我们观察到与循环白细胞介素(IL)-8、IL-10、IL-17 和空肠呈正相关。总之,肝脏中的 OLFM2 似乎在 NAFLD 进展中发挥重要作用,而空肠中的 OLFM4 可能参与与肠道菌群失调相关的炎症事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d24c/9267292/93db9c90c497/ijms-23-07442-g001.jpg

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