Introduction and Objective: Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes and other metabolic disorders, including steatotic liver disease. However, its short half-life necessitates multiple daily injections, resulting in poor patient compliance, limited efficacy, and increased treatment costs. To address this problem, we introduce a novel drug delivery strategy based on the genetic fusion of an albumin binding domain (ABD) and an anti-neonatal Fc receptor (FcRn) affibody (AFF) to therapeutic proteins.Methods: In this study, we investigated the effects of EX-ABD-AFF on high fat diet (HFD)-induced steatotic liver disease in mice.Results: EX-ABD-AFF significantly enhanced insulin secretion while reducing fat mass and liver weight. Notably, it markedly decreased lipid accumulation in the liver and improved liver function. Additionally, EX-ABD-AFF significantly increased both serum and hepatic LCN2 levels.Conclusion: Collectively, these findings suggest that EX-ABD-AFF enhances insulin release in pancreatic β-cells and that hepatic LCN2 may play a role in improving steatotic liver.
G. Roh: None.
National Research Foundation of Korea (RS-2023-00219399)
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