非肥胖患者的非酒精性脂肪肝 (NAFLD) 具有独特的病理生理学特征，与 2 型糖尿病 (T2DM) 表现出共同的免疫学联系。本研究旨在阐明 Toll 样受体 2 (TLR2) 介导的免疫调节及其与成纤维细胞生长因子受体 4 (FGFR4) 及其配体成纤维细胞生长因子 19 (FGF19) 的关联在 NAFLD 发病机制中的作用。在征得同意和临床记录的情况下，从 NAFLD 患者 (n = 90)、NAFLD 合并 T2DM (n = 90) 和健康队列 (n = 90) 中采集血液样本。采用实时聚合酶链反应（PCR）、酶联免疫分析（ELIZA）和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析信使核糖核酸（mRNA）、蛋白表达和基因多态性。遗传分析显示，与对照组相比，这两种情况下 FGFR4 基因中存在变异等位基因 (A)。与伴有 T2DM 的 NAFLD 相比，不伴有 T2DM 的 NAFLD 中 FGF19 和 TLR2 的 mRNA 表达显着上调。与对照组相比，两个疾病组的肿瘤坏死因子-α (TNF-α) 和白介素-12 (IL-12) 均显示上调，而与其他两个组相比，IL-10 在 NAFLD 合并 T2DM 中显示显着下调。 FGF19 和 TLR2 之间的相关性分析显示，无论是否患有 T2DM，NAFLD 均存在显着正相关。与无 T2DM 的 NAFLD 相比，伴 T2DM 的 NAFLD 中 Th1:Th2 比率显着上调。 总之，血清内毒素水平升高似乎有助于 NAFLD 和 T2DM 的发展。 FGF19 上调似乎可以预防 NAFLD 患者发展为 T2DM。不伴 T2DM 的 NAFLD 中 TLR2、TNF-α 和 IL-12 表达较高，提示其发病机制存在 Th1 偏向性，而伴 T2DM 的 NAFLD 中 IL-10 表达降低则意味着在这种情况下 Th1 状态更加偏向。© 2024。印度胃肠病学会。

Non-alcoholic fatty liver disease (NAFLD) in non-obese patients is pathophysiologically distinct, exhibiting common immunological link with type-2 diabetes mellitus (T2DM). This study aims to delineate the role of Toll-like receptor 2 (TLR2)-mediated immuno-modulation along with its association with fibroblast growth factor receptor 4 (FGFR4) and its ligand fibroblast growth factor 19 (FGF19) in the pathogenesis of NAFLD without or with T2DM.Blood samples were collected from patients with NAFLD (n = 90), NAFLD with T2DM (n = 90) and healthy cohorts (n = 90) with consent and clinical records. Real-time polymerase chain reaction (PCR), enzyme-linked immunoassay (ELIZA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to analyze messenger ribonucleic acid (mRNA), protein expression and gene polymorphism.The molecular genetic analysis revealed the prevalence of variant allele(A) in FGFR4 gene in both cases compared to controls. The mRNA expression of FGF19 and TLR2 exhibited significant upregulation in NAFLD without T2DM compared to NAFLD with T2DM. Tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) showed upregulation in both disease cohorts compared to control while IL-10 showed significant downregulation in NAFLD with T2DM compared to the other two cohorts. Correlation analysis between FGF19 and TLR2 revealed significant positive association in both NAFLD with and without T2DM. The Th1:Th2 ratio showed significant upregulation in NAFLD with T2DM compared to NAFLD without T2DM.In conclusion, elevated serum endotoxin levels appear to contribute to NAFLD and T2DM development. Upregulated FGF19 seems to be protective against developing T2DM in NAFLD patients. Higher TLR2, TNF-α and IL-12 expression in NAFLD without T2DM suggests a Th1 bias in its pathogenesis, while reduced IL-10 in NAFLD with T2DM implies a more skewed Th1 state in this condition.© 2024. Indian Society of Gastroenterology.