title: A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice.
abstract: Bacterial lipopolysaccharide (LPS), also known as endotoxin, induces profound anorexia. However, the LPS-provoked pro-inflammatory signaling cascades and the neural mechanisms underlying the development of anorexia are not clear. Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth, and protein synthesis. This study aimed to determine whether the mTOR pathway is involved in LPS-induced anorexia. Effects of LPS on hypothalamic gene/protein expression in mice were measured by RT-PCR or western blotting analysis. To determine whether inhibition of mTOR signaling could attenuate LPS-induced anorexia, we administered an i.c.v. injection of rapamycin, an mTOR inhibitor, on LPS-treated male mice. In this study, we showed that LPS stimulates the mTOR signaling pathway through the enhanced phosphorylation of mTOR(Ser2448) and p70S6K(Thr389). We also showed that LPS administration increased the phosphorylation of FOXO1(Ser256), the p65 subunit of nuclear factor kappa B (P<0.05), and FOXO1/3a(Thr) (24) (/) (32) (P<0.01). Blocking the mTOR pathway significantly attenuated the LPS-induced anorexia by decreasing the phosphorylation of p70S6K(Thr389), FOXO1(Ser256), and FOXO1/3a(Thr) (24) (/) (32). These results suggest promising approaches for the prevention and treatment of LPS-induced anorexia.
authors.affiliation: Shandong Key Lab for Animal Biotechnology and Disease ControlDepartment of Animal Science, Shandong Agricultural University, No. 61, Daizong Street, Taian, Shandong 271018, People's Republic of China.
authors.forename: Yunshuang
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Shandong Key Lab for Animal Biotechnology and Disease ControlDepartment of Animal Science, Shandong Agricultural University, No. 61, Daizong Street, Taian, Shandong 271018, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shandong Key Lab for Animal Biotechnology and Disease ControlDepartment of Animal Science, Shandong Agricultural University, No. 61, Daizong Street, Taian, Shandong 271018, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Shandong Key Lab for Animal Biotechnology and Disease ControlDepartment of Animal Science, Shandong Agricultural University, No. 61, Daizong Street, Taian, Shandong 271018, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Song
authors.affiliation: Shandong Key Lab for Animal Biotechnology and Disease ControlDepartment of Animal Science, Shandong Agricultural University, No. 61, Daizong Street, Taian, Shandong 271018, People's Republic of China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Shandong Key Lab for Animal Biotechnology and Disease ControlDepartment of Animal Science, Shandong Agricultural University, No. 61, Daizong Street, Taian, Shandong 271018, People's Republic of China hailin@sdau.edu.cn.
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
mesh_terms: D000818:Animals; D000855:Anorexia / Q000276:immunology / Q000382:microbiology*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases
keywords: FoxO1; LPS; NFκB; anorexia; hypothalamus; mTOR; rapamycin