title: Dietary gossypol suppressed postprandial TOR signaling and elevated ER stress pathways in turbot (Scophthalmus maximus L.).
abstract: Gossypol is known to be a polyphenolic compound toxic to animals. However, its molecular targets are far from fully characterized. To evaluate the physiological and molecular effects of gossypol, we chose turbot (Scophthalmus maximus L.), a carnivorous fish, as our model species. Juvenile turbots (7.83 ± 0.02 g) were fed diets containing gradient levels of gossypol at 0 (G0), 600 (G1), and 1,200 (G2) mg/kg diets for 11 wk. After the feeding trial, fish growth, body protein, and fat contents were significantly reduced in the G2 group compared with those of the G0 group (P < 0.05). Gossypol had little impact on digestive enzyme activities and intestine morphology. However, gossypol caused liver fibrosis and stimulated chemokine and proinflammatory cytokine secretions. More importantly, gossypol suppressed target of rapamycin (TOR) signaling and induced endoplasmic reticulum (ER) stress pathway in both the feeding experiment and cell cultures. Our results demonstrated that gossypol inhibited TOR signaling and elevated ER stress pathways both in vivo and in vitro, thus providing new mechanism of action of gossypol in nutritional physiology.
authors.affiliation: Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture, Ocean University of China, Qingdao, China.
authors.forename: Fuyun
authors.initials: F
authors.lastname: Bian
authors.affiliation: Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture, Ocean University of China, Qingdao, China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture, Ocean University of China, Qingdao, China.
authors.forename: Mingsan
authors.initials: M
authors.lastname: Man
authors.affiliation: Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture, Ocean University of China, Qingdao, China.
authors.forename: Kangsen
authors.initials: K
authors.lastname: Mai
authors.affiliation: Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture, Ocean University of China, Qingdao, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture, Ocean University of China, Qingdao, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture, Ocean University of China, Qingdao, China hegen@ouc.edu.cn.
authors.forename: Gen
authors.initials: G
authors.lastname: He
mesh_terms: D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005355:Fibrosis; D005412:Flatfishes; D006072:Gossypol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D019518:Postprandial Period; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects* / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects; D015027:Zebrafish
chemical_list: D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; D006072:Gossypol
keywords: ER stress; TOR; gossypol, turbot (Scophthalmus maximus L.); liver fibrosis