Ghrelin and LEAP2: Their Interaction Effect on Appetite Regulation and the Alterations in Their Levels Following Bariatric Surgery

Background and Objectives: Ghrelin plays key roles in appetite regulation, involving both homeostatic and hedonic pathways. In obesity, its metabolism is affected by alterations in neural and hormonal responses. Liver-Enriched Antimicrobial Peptide 2 (LEAP2), recently identified as an endogenous ghrelin receptor antagonist, has emerged as a potential regulator of appetite and energy balance, and bariatric surgery is known to induce changes in this system. In this review, we aimed to evaluate the roles of acyl ghrelin, des-acyl ghrelin, and LEAP2 in food intake regulation and summarize findings on the alterations in their levels after bariatric surgery. Materials and Methods: We conducted a narrative review of human and animal studies published in the literature investigating the roles of acyl ghrelin, des-acyl ghrelin, and LEAP2 in food intake regulation, as well as changes in their levels in obesity and following bariatric surgery. Results: Alterations in the ghrelin system, i.e., the acyl ghrelin and des-acyl ghrelin isoforms and LEAP2, in obesity have been reported. Experimental studies have shown that LEAP2 administration reduces food intake and body weight by suppressing ghrelin-induced food intake. Most studies have found marked reductions in fasting acyl ghrelin after sleeve gastrectomy, more so than after Roux-en-Y gastric bypass. Conclusions: In obesity, altered neural and hormonal responses to food also affect ghrelin metabolism, with significant deviations in acyl ghrelin levels and impaired appetite regulation mechanisms. Unlike ghrelin, LEAP2 levels tend to be elevated in obesity. While changes in acyl ghrelin and des-acyl ghrelin isoforms, particularly after sleeve gastrectomy, are well documented, data on LEAP2 remain limited. Further research is needed to better define the role of LEAP2 in ghrelin-mediated food intake and its potential as a therapeutic target in obesity.