Interplay Between Enteroendocrine Hormone (Leptin) and Adipokines (Ghrelin and Adiponectin) with Gastric Expression of FTO and MC4R Genes

Abstract

Abstract Obesity is a complex, multifactorial disease influenced by genetic, hormonal, and metabolic factors. The fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes have been implicated in body weight regulation through gut–brain signaling and their interactions with adipokines and enteroendocrine hormones. This study investigated the association between gastric expression of FTO and MC4R genes and circulating levels of leptin, adiponectin, and ghrelin in individuals with and without obesity. We conducted a case–control study including 50 patients with obesity undergoing sleeve gastrectomy and 50 controls undergoing diagnostic endoscopy. Gastric tissue gene expression was assessed by qRT-PCR, and serum hormone levels were quantified using ELISA. Inverse propensity score weighting was used to adjust for age and sex. FTO expression was significantly upregulated in patients with obesity (fold-change: 5.8 vs. 1.0, p  < 0.001), showing a parallel elevation with adiponectin and BMI at the group level. In contrast, MC4R expression was significantly downregulated (fold-change: 0.1 vs. 1.0, p  < 0.001), and positively associated with HOMA-IR and showed a borderline positive trend with fasting blood glucose ( p  = 0.074). Adiponectin levels were paradoxically elevated in the obesity group and correlated with both BMI and HDL. Leptin and ghrelin levels showed no significant group differences. These findings suggest that altered gastric expression of FTO and MC4R may contribute to obesity-related metabolic disturbances through peripheral adipokine pathways. Further investigation into tissue-specific gene–hormone interactions may inform novel therapeutic strategies for obesity.