IGFBP-3 promotes cachexia-associated lipid loss by suppressing insulin-like growth factor/insulin signaling

Background:Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia.In addition to systemic immune/inflammatory effects in response to tumor progression,tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss.However,the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood.Methods:The yki-gut tumors were induced in fruit flies.Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3(IGFBP-3)treated cells.Immunoblotting was used to display phenotypes of tumor cells and adipocytes.Quantitative polymerase chain reaction(qPCR)analysis was carried out to examine the gene expression levels such as Acc1,Acly,and Fasn et al.Results:In this study,it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes.IGFBP-3,which is highly expressed in cachectic tumor cells,antagonized insulin/IGF-like signaling(IIS)and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes.Conditioned medium from cachectic tumor cells,such as Capan-1 and C26 cells,contained excessive IGFBP-3 that potently induced lipolysis in adipocytes.Notably,neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes.Furthermore,cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS,ensuring their escape from IGFBP-3-associated growth suppression.Finally,cachectic tumor-derived ImpL2,the IGFBP-3 homolog,also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila.Most importantly,IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients,especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients.Conclusion:Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.

Performance of pond–wetland complexes as a preliminary processor of drinking water sources

Shijiuyang Constructed Wetland（110 hm^2） is a drinking water source treatment wetland with primary structural units of ponds and plant-bed/ditch systems. The wetland can process about 250,000 tonnes of source water in the Xincheng River every day and supplies raw water for Shijiuyang Drinking Water Plant. Daily data for 28 months indicated that the major water quality indexes of source water had been improved by one grade. The percentage increase for dissolved oxygen and the removal rates of ammonia nitrogen, iron and manganese were 73.63%, 38.86%, 35.64%, and 22.14% respectively. The treatment performance weight of ponds and plant-bed/ditch systems was roughly equal but they treated different pollutants preferentially. Most water quality indexes had better treatment efficacy with increasing temperature and inlet concentrations. These results revealed that the pond–wetland complexes exhibited strong buffering capacity for source water quality improvement. The treatment cost of Shijiuyang Drinking Water Plant was reduced by about 30.3%. Regional rainfall significantly determined the external river water levels and adversely deteriorated the inlet water quality, thus suggesting that the ＂hidden＂ diffuse pollution in the multitudinous stream branches as well as their catchments should be the controlling emphases for river source water protection in the future. The combination of pond and plant-bed/ditch systems provides a successful paradigm for drinking water source pretreatment. Three other drinking water source treatment wetlands with ponds and plant-bed/ditch systems are in operation or construction in the stream networks of the Yangtze River Delta and more people will be benefited.