Effects of catalpol on glycolipid homeostasis and lifespan of Drosophila melanogaster

Abstract Glycolipid metabolism is a core regulatory link in the energy homeostasis and physiological functions of insects, directly affecting their survival, development, reproduction and environmental adaptability. Catalpol, the main active component of Rehmannia glutinosa , possesses multiple pharmacological activities, such as antioxidation, anti‐inflammation and regulation of glycolipid metabolism. However, the specific regulatory mechanism of its effect on insect metabolism remains unclear. In this study, Drosophila melanogaster was used as the model organism to systematically explore the effects of catalpol on glycolipid metabolism, growth and development, motor ability and lifespan of female adults, as well as its underlying molecular mechanism. At the molecular level, catalpol significantly enhances glucose catabolism, as demonstrated by increased activity of both soluble and membrane‐bound trehalase and upregulation of the Tret1‐1 gene. Concurrently, it dynamically regulated lipid metabolism, significantly increasing the content of free fatty acids and triglycerides. This finding, coupled with the upregulation of key lipolytic genes such as hormone‐sensitive lipase ( HSL ), indicates accelerated fat turnover. These metabolic modulations translated into significant phenotypic improvements. Catalpol treatment promoted insect growth and development, as evidenced by increased body weight, abdominal size and wing area. Furthermore, it enhanced their motor ability, shown by improved climbing, and extended their average lifespan and survival rate, suggesting a delay in ageing. In conclusion, this study elucidates a novel regulatory model, wherein catalpol dynamically modulates both glucose and lipid metabolism, leading to improved growth, enhanced motor function and extended lifespan in D. melanogaster . Our findings provide initial insights into the intricate mechanism‐phenotype connection and provide compelling experimental evidence for catalpol's potential as an insect physiological regulator. This research not only offers new perspectives on insect energy homeostasis but also lays a foundation for its application in agricultural pest control and beneficial insect breeding.