👤 Noha A El-Banna

The fat mass and obesity-associated (FTO) and melanocortin-4 receptor (MC4R) genes have been implicated in the pathophysiology of obesity. However, their regulatory behavior in human gastric tissue and association with postoperative weight loss following metabolic and bariatric surgery (MBS) remain unclear. In this prospective case-control study, gastric tissue from 50 patients with obesity undergoing laparoscopic sleeve gastrectomy and 48 non-obese controls was analyzed for FTO and MC4R mRNA expression using quantitative PCR. Adjusted Inverse propensity score weighting (IPSW-adjusted) and age-/sex-adjusted linear regression were applied. Receiver operating characteristic (ROC) curves were used to evaluate discriminatory thresholds. Correlation with 12-month percent total weight loss (%TWL) was assessed. FTO expression was significantly upregulated (mean fold-change: 4.68, p < 0.001) and MC4R downregulated (mean fold-change: - 0.91, p < 0.001) in patients with obesity. ROC analysis identified thresholds of > 1.515 for FTO (AUC = 1.00) and < 0.525 for MC4R (AUC = 1.00), both with high sensitivity and specificity. No significant correlation was observed between gene expression and %TWL at 12-month follow-up. Gastric expression of FTO and MC4R accurately discriminates between individuals with and without obesity but does not predict postoperative weight loss outcomes after sleeve gastrectomy. These findings indicate diagnostic potential, whereas prognostic value remains unsubstantial. Show less

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, Show less

Treatments are emerging for the neuronal ceroid lipofuscinoses (NCLs), a group of similar but genetically distinct lysosomal storage diseases. Clinical ratings scales measure long-term disease progression and response to treatment but clinically useful biomarkers have yet to be identified in these diseases. We have conducted proteomic analyses of brain and cerebrospinal fluid (CSF) from mouse models of the most frequently diagnosed NCL diseases: CLN1 (infantile NCL), CLN2 (classical late infantile NCL) and CLN3 (juvenile NCL). Samples were obtained at different stages of disease progression and proteins quantified using isobaric labeling. In total, 8303 and 4905 proteins were identified from brain and CSF, respectively. We also conduced label-free analyses of brain proteins that contained the mannose 6-phosphate lysosomal targeting modification. In general, we detect few changes at presymptomatic timepoints but later in disease, we detect multiple proteins whose expression is significantly altered in both brain and CSF of CLN1 and CLN2 animals. Many of these proteins are lysosomal in origin or are markers of neuroinflammation, potentially providing clues to underlying pathogenesis and providing promising candidates for further validation. Show less