Endurance exercise prevents genetic obesity, exercise tolerance limitation, and cardiac dysfunction induced by knockdown of Akh gene in different tissues in Drosophila

Abstract The Adipokinetic hormone (Akh) is a key regulator of energy metabolism in Drosophila melanogaster, analogous to glucagon in mammals. Aerobic endurance exercise is considered to be an important means to prevent and reduce obesity and its related complications, but it is still unclear whether it can effectively combat obesity and obesity-related exercise impairment and heart dysfunction induced by Akh genetic knockdown. In this study, Akh-UAS-RNAi/Ppl-Gal4 and Akh-UAS-RNAi/Mef2-Gal4 systems were constructed in F1 generation Drosophila through hybridization, and the Akh gene was knocked down in adipose tissue and muscle tissue. Experimental flies underwent an endurance exercise intervention lasting 3 weeks starting at 1 week of age. The results showed that the knockdown of Akh in both adipose tissue and skeletal muscle tissue significantly increased body weight, triglyceride levels, the expression of Bmm gene and Mdy gene, and MDA level, and it also significantly decreased exercise endurance, cardiac fractional shortening, SOD level, and the expression of Srl gene. Moreover, the microscopic images of oil red O staining and the ultraimages of transmission electron microscopy indicated that Akh knockdown led to the increase of lipid dropper accumulation and the destruction of mitochondrial structure. Importantly, endurance exercise effectively prevented these changes induced by Akh knockdown in adipose tissue and muscle tissue by up regulating Akh gene. Therefore, our present findings demonstrated for the first time that endurance exercise could act as the upstream regulator of Akh gene in adipose tissue and muscle tissue, improve obesity, exercise tolerance limitation, and cardiac dysfunction induced by knockdown of Akh gene via activating Akh/Bmm/Mdy pathway, Akh/srl pathway, and Akh/SOD/MDA pathway.