Amphibian Skin–Derived Peptides as Emerging Therapeutic Scaffolds for Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD)

Metabolic dysfunction–associated steatotic liver disease (MASLD) is now the most common chronic liver disorder worldwide. Once started with hepatic steatosis, it can progress to metabolic dysfunction–associated steaohepatitis (MASH), cirrhosis, and even hepatocellular carcinoma. Insulin resistance is a major driver of hepatic lipogenesis in this disease context. Gut barrier dysfunction also contributes to the progression to MASH by allowing bacterial lipopolysaccharide (LPS) to breach into the hepatic tissues. Amphibian skin secretion peptides (ASSPs) are therefore of particular interest, given their combined metabolic and antimicrobial activities. Some ASSPs enhance glucose-stimulated insulin secretion and GLP-1 release, whereas others attenuate LPS-driven inflammatory signaling. This review introduces these ASSPs with a focus on their insulinotropic/incretinotropic and immunomodulatory activities. Also, in the latter part, pharmaceutical strategies to improve blood circulation time and structural stability would be discussed.