1. Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Center for global health, Nanjing Medical University, Nanjing, Jiangsu, China.
2. Department of endocrinology, the Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
3. Key Laboratory of Rare Metabolic Disease, Nanjing Medical University, Nanjing, Jiangsu, China.
4. Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Queensland, Australia.
5. State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
6. Department of Pathogen Biology, Nantong University. Nantong, Jiangsu, China.
#These authors contributed equally to this work.
Background: The host-parasite relationship is based on subtle interplay between parasite survival strategies and host defense mechanisms. It is well known that helminth infection, which afflicts more than one billion people globally, correlates with a decreased prevalence of obesity. Dissecting the underlying mechanisms can provide new targets for treating obesity from the host-parasite interaction perspective.
Methods: C57BL/6 mice received a normal or high-fat diet (HFD) with or without Sjp40 (one main component of schistosome-derived soluble egg antigens) treatment. Both the loss and gain-of-function experiments by the inhibitor suppression and lentivirus treatment of miR-802 were utilized to elucidate the role of miR-802/AMPK axis in host lipid metabolism. Hepatocyte lipogenesis assay and metabolic parameters were assessed both in vivo and in vitro. The potential interactions among Sjp40, CD36, miR-802, Prkab1, and AMPK were clarified by pull-down, miRNA expression microarray, quantitative RT-PCR, dual-luciferase reporter assay, and western blotting analysis.
Results: We showed a link between decreased miR-802 and impaired lipid metabolism in Schistosoma japonicum infected mice. The decreased miR-802 promotes murine Prkab1 or human Prkaa1 expression, respectively, which increases levels of phosphorylated AMPK, resulting in a decrease in hepatic lipogenesis. Also, injection with schistosome-derived soluble egg antigens (SEA) attenuated metabolism. We demonstrated that Sjp40 as a main component of SEA interacted with CD36 on hepatocytes to inhibit miR-802, resulting in the activation of AMPK pathway and subsequent attenuation of lipogenesis.
Collectively: Our study reveals the significant role of miR-802/AMPK axis in hepatic lipid metabolism and identifies the therapeutic potential of Sjp40 in treating obesity-related fatty liver.
Keywords: miR-802, Sjp40, Schistosoma japonicum, AMPK, lipid metabolism