title: Leptin exerts proliferative and anti-apoptotic effects on goose granulosa cells through the PI3K/Akt/mTOR signaling pathway.
abstract: Leptin was known as a pivotal regulator for the control of food intake and energy expenditure. However, leptin has also been found to be involved in the regulation of female reproductive system through interactions with pathways in the hypothalamic-hypophyseal axis and direct action at the ovarian level. In the present study, granulosa cells from goose ovarian preovulatory (F1-F3) follicles were cultured with leptin (0, 1, 10 or 100ng/ml). The proliferative and anti-apoptotic actions of leptin in granulosa cells were revealed by CCK-8, BrdU and TUNEL assays. Quantitative real-time PCR and Western blot analyses further indicated that leptin treatment led to increased expression of cyclin D1, cyclin D2, cyclin D3 and bcl-2, and decreased expression of p21 and caspase-3. The effects were involved in the activation of the PI3K/Akt/mTOR signaling pathway, as leptin treatment enhanced the expression of PI3K, Akt1, Akt2, Raptor, mTOR, S6K and p-S6K. Moreover, blockade of the PI3K/Akt/mTOR pathway attenuated the influences of leptin on proliferation and apoptosis of granulosa cells, considering that activated factors by leptin were inhibited in the presence of either 20μM LY294002 (a PI3K inhibitor) or 10μM rapamycin (an mTOR inhibitor). In addition, leptin had a modulatory effect on the expression of its receptor at the transcriptional and translational levels, and blockade of PI3K/Akt/mTOR inhibited both basal and leptin-induced Lepr gene and protein expression. These findings suggest that leptin exerts its proliferative and anti-apoptotic effects on goose granulosa cells through the PI3K/Akt/mTOR signaling pathway via interaction with its receptor.
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wen
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Shenqiang
authors.initials: S
authors.lastname: Hu
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Han
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gan
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gou
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Hehe
authors.initials: H
authors.lastname: Liu
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Hengyong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an, Sichuan 625014, PR China. Electronic address: wjw2886166@163.com.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005777:Geese / Q000378:metabolism*; D006107:Granulosa Cells / Q000166:cytology* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D054411:Receptors, Leptin; D058570:TOR Serine-Threonine Kinases
keywords: Apoptosis; Goose; Leptin; PI3K; Proliferation; mTOR