A HORMONAL AND CLINICAL INVESTIGATION OF SURGICAL FAT REMOVAL

Abstract

Obesity remains one of the most pressing global health challenges, with Qatar among the most affected regions. While bariatric surgery is well established for inducing durable weight loss, and newer pharmacologic agents such as glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) agonists continue to advance metabolic care, the hormonal and metabolic consequences of surgical subcutaneous fat removal (SSFR), a common procedure following massive weight loss as well as in aesthetic practice, remain poorly understood. Given the endocrine functions of both adipose tissue and the gastrointestinal tract, this thesis investigates the hormonal, metabolic, and psychological adaptations associated with SSFR within a combined framework of evidence synthesis, quasi-experimental measurement, and mechanistic exploration. This thesis is structured around three major themes. Theme 1 synthesizes global evidence from 59 studies reporting hormonal trajectories after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). Using robust error meta-regression (REMR), the analysis demonstrates consistent increases in GLP-1 and peptide YY (PYY), sustained reductions in GIP after RYGB, procedure-specific ghrelin trajectories, and early leptin reductions preceding weight loss, suggesting enhanced leptin sensitivity. Together, these findings identify the durable hormonal signature of bariatric surgery and establish the metabolic context into which SSFR patients may later fall. Theme 2 presents a quasi-experimental study of patients undergoing SSFR procedures at Hamad Medical Corporation, assessed at four time points from pre-operative evaluation to ten months post-surgery. This work validates bioelectrical impedance analysis (Tanita) as a reliable measure of fat mass change following SSFR and reveals that early postoperative reductions in fat mass correlate with excised tissue weight. A parallel study of oral glucose tolerance test (OGTT) physiology demonstrates that SG patients exhibit altered postprandial glucose excursions with an increased likelihood of late-onset, non-severe hypoglycemia. Analytical comparison supports Doi's weighted average glucose (dwAG) as a simplified, clinically useful glycemic metric. These contributions establish the metabolic baseline against which future hormonal adaptations are interpreted. Theme 3 investigates hormonal predictors of body composition, insulin sensitivity, appetite, and psychological well-being. Using multiplex assays and multivariable logistic modeling, this work identifies, for the first time, specific adipokines and gut hormones that predict the lean phenotype (notably amylin) and the insulin-sensitive phenotype (GIP as the strongest independent predictor). Further analyses reveal a complex hormonal network regulating leptin sensitivity, with spexin emerging as a biomarker of the leptin-responsive state and modulated by GLP-1, GIP, and fat mass. In the domain of appetite, reduced post-SSFR appetite is strongly associated with lower GIP levels, supporting a gut-brain axis role for GIP. Finally, SSFR is shown to significantly improve psychological outcomes-across the Appearance Anxiety Inventory (AAI), the Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, and the Generalized Anxiety Disorder-7 (GAD-7) scale for anxiety-with hormonal and surgical factors jointly predicting mental health improvements. Overall, this thesis identifies key hormonal regulators of fat mass, insulin sensitivity, appetite, and psychological outcomes in humans and demonstrates that SSFR carries previously underrecognized metabolic and psychosocial benefits. The findings advance understanding of leptin resistance mechanisms, highlight novel hormonal biomarkers for metabolic phenotyping, and provide a scientific basis for integrating SSFR into comprehensive metabolic care. This body of work establishes new mechanistic hypotheses for future research and offers clinically relevant insights for plastic surgery, metabolic medicine, and obesity management.