Role of lncRNAs H19, KCNQ1OT1 and SRA in relation to peroxisome proliferator-activated receptor gamma in the occurrence and progression of non-alcoholic fatty pancreas disease in obese and non-obese Egyptian patients.

LncRNAs are key regulators of gene expression in inflammatory diseases, offering promising avenues for diagnostic, prognostic, and therapeutic applications. Identification of disease-specific lncRNAs for non-alcoholic fatty pancreas disease (NAFPD) remains a challenge due to its complex pathogenesis. This study evaluated the expression of lncRNAs; H19, KCNQ1OT1, and SRA, and their target, peroxisome proliferator-activated receptor gamma (PPARγ), to elucidate the potential molecular mechanism in NAFPD. 112 NAFPD patients and 50 age- and sex-matched controls were recruited, with both groups subcategorized into obese and non-obese. Data revealed significant upregulation of lncRNAs and PPARγ mRNA, coupled with marked downregulation of miR-138, in both NAFPD subgroups and obese controls. Serum heat shock protein 70 (HSP70), phospholipase A2 (PLA2), chemerin and matrix metalloproteinase-9 (MMP-9) were significantly elevated, particularly in obese patients. Potent positive correlations existed among lncRNAs, PPARγ, HSP70, PLA2, chemerin, MMP9, BMI and HOMA-IR, suggesting a tightly linked regulatory network. All markers displayed a negative correlation with miR-138. H19 and KCNQ1OT1 demonstrated superior diagnostic and predictive potentials for early NAFPD detection while SRA emerged as a promising predictor of disease progression. Machine learning models were also employed to validate the diagnostic and predictive strength of the identified biomarkers. These findings underscore a complex, obesity-driven interplay among the studied lncRNAs/miR-138/PPARγ, contributing to NAFPD pathogenesis through inflammatory signaling, insulin resistance, and tissue remodeling.