Abstract
The Adipokinetic hormone (Akh), a functional analog of mammalian glucagon, plays a key role in regulating energy metabolism in Drosophila. Although exercise is recognized as an important intervention for preventing and alleviating obesity-related complications, its efficacy against obesity induced by Akh gene deficiency remains unclear. In this study, the Akh gene was knocked down systemically and specifically in the corpora cardiaca (CC) using Act-gal4/Akh-UAS-RNAi and Akh-gal4/Akh-UAS-RNAi systems in flies, and these flies were followed by a two-week exercise intervention. The results showed Akh knockdown induced obesity phenotypes, including significantly increased body weight and triglyceride levels, and concurrently impaired skeletal muscle and cardiac function-manifested as reduced climbing speed, climbing endurance, and cardiac shortening fraction, along with elevated heart rate. Mechanistically, these effects were associated with upregulated systemic FASN1/Mdy/triglyceride process and lipotoxicity (MDA), as well as downregulated mitochondrial (PGC-1α) and contractile (Mhc) markers in muscle. Exercise intervention ameliorated the obesity phenotype and was correlated with increased Akh expression. These findings confirm that Akh gene deficiency contributes to hereditary obesity and obesity-related dysfunction of skeletal muscle and heart, and demonstrate that exercise can serve as a therapeutic strategy to counteract impairments resulting from Akh knockdown, suggesting its potential relevance for treating human obesity linked to glucagon-related genetic defects.
