Abstract
Objectives: Gomisin N is a lignin derived from Schisandra chinensis that was reported to exhibit hepato-protective, anticancer, and anti-inflammatory effects. However, its role in whole body energetic homeostasis remains unclear. Drosophila melanogaster shares the majority of metabolic functions in vertebrates, including conserved signaling pathways for lipid metabolism and glucose homeostasis, making it a suitable model system to study the effects of signaling molecules and their modifiers in vivo. In this study, we employed fruit flies as a diet-induced obese model to elucidate the effects of Gomisin N on lipid and glucose metabolism Methods: We have characterized the adolescent fly phenotypes in triglyceride levels and lifespan when reared on a high-fat diet, with or without Gomisin N. Results: Constant exposures of flies to a high-fat diet resulted in significantly increased triglyceride levels along with a shortened life span. Importantly, an administration of Gomisin N to this group of flies lowered their body weight and total triglyceride levels and improved their lifespan. To pinpoint the molecular mechanism of the anti-obesity effects of Gomisin N, we adopted a cell-based assay using mouse pancreatic β-cells exposed to a metabolic stress with antimycin. The drug-induced metabolic stress increased ER stress proteins as well as relevant apoptotic markers. Importantly, a treatment of these pancreatic β-cells with Gomisin N prevented ER stress-induced apoptosis and increased autophagy. Conclusions: Taken together, these in vivo and in vitro findings suggest that Gomisin N could serve as a useful agent for prevention and treatment of obesity.