Leap2, also known as Liver Enriched Antimicrobial Peptide 2, was initially identified as an antimicrobial peptide. It has gained significant attention for its key role in regulating energy metabolism. Leap2 interacts with the ghrelin hormone, acting as an inhibitor of ghrelin. By doing so, it reduces food intake and influences energy balance. It also impacts insulin secretion, potentially being involved in glucose metabolism and insulin sensitivity [1].

In LEAP2-KO mouse models, several important findings have emerged. LEAP2-KO mice were more sensitive to subcutaneous ghrelin, with acyl-ghrelin stimulating food intake at lower doses compared to wild-type littermates. LEAP2 deletion also increased body weight, food intake, lean mass, hepatic fat, and body length in female mice on a long-term high-fat diet. This was due to lowered energy expenditure, reduced locomotor activity, and increased food intake. In cancer-related anorexia-cachexia syndrome mouse models, LEAP2 deletion lessened reductions in tumor-free body weight and fat mass and increased food intake [2,3].

In conclusion, Leap2 plays essential roles in energy metabolism, food intake regulation, and glucose metabolism. Studies using LEAP2-KO mouse models have revealed its significance in conditions such as obesity-related metabolic disorders and cancer-related anorexia-cachexia syndrome, providing insights into potential therapeutic targets for these diseases.