PMID- 22508056 OWN - NLM STAT- MEDLINE DCOM- 20120809 LR - 20220318 IS - 1421-9778 (Electronic) IS - 1015-8987 (Print) IS - 1015-8987 (Linking) VI - 29 IP - 3-4 DP - 2012 TI - mTOR-dependent modulation of gastric nesfatin-1/NUCB2. PG - 493-500 LID - 10.1159/000338503 [doi] AB - BACKGROUND: Nesfatin-1, an 82 amino acid peptide derived from the prohormone nucleobindin-2 (NUCB2), is a novel satiety hormone acting through a leptin-independent mechanism in the hypothalamus. The mechanisms by which production of nesfatin-1/NUCB2 is regulated remain unknown. METHODS: Nesfatin-1/NUCB2 mRNA and immunoreactivity were examined in gastric tissue and Min-6 cells by RT-PCR and immunofluorescent staining or Western blotting. RESULTS: Nesfatin-1/NUCB2 is co-localized with pS6K1, the downstream target of mammalian target of rapamycin (mTOR), in gastric X/A like cells. A parallel relationship between gastric mTOR signaling and nesfatin-1/NUCB2 was observed during changes in energy status. Both mTOR activity and gastric nesfatin-1/NUCB2 were down-regulated by fasting, and returned to basal levels with re-feeding. In high fat diet induced obese mice, gastric mTOR signaling and nesfatin-1/NUCB2 were increased. Inhibition of the gastric mTOR signaling by rapamycin attenuated the expression of gastric nesfatin-1/NUCB2 mRNA and protein in both lean and obese mice. Attenuation of mTOR activity by rapamycin or over-expression of TSC1 or TSC2 reduced the expression of nesfatin-1/NUCB2 in Min-6 cells, suggesting a direct effect of mTOR signaling. CONCLUSION: Gastric mTOR is a gastric energy sensor whose activity is linked to the regulation of gastric nesfatin-1/NUCB2. CI - Copyright (c) 2012 S. Karger AG, Basel. FAU - Li, Ziru AU - Li Z AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China. FAU - Xu, Geyang AU - Xu G FAU - Li, Yin AU - Li Y FAU - Zhao, Jing AU - Zhao J FAU - Mulholland, Michael W AU - Mulholland MW FAU - Zhang, Weizhen AU - Zhang W LA - eng GR - R01 DK043225/DK/NIDDK NIH HHS/United States GR - R01 DK054032/DK/NIDDK NIH HHS/United States GR - R37 DK043225/DK/NIDDK NIH HHS/United States GR - R01DK043225/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120403 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Calcium-Binding Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nucb1 protein, mouse) RN - 0 (Nucleobindins) RN - 0 (RNA, Messenger) RN - 0 (Tsc1 protein, mouse) RN - 0 (Tsc2 protein, mouse) RN - 0 (Tuberous Sclerosis Complex 1 Protein) RN - 0 (Tuberous Sclerosis Complex 2 Protein) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Blotting, Western MH - Calcium-Binding Proteins/genetics/*metabolism MH - Cell Line MH - DNA-Binding Proteins/genetics/*metabolism MH - Diet, High-Fat/adverse effects MH - Endocrine Cells/metabolism MH - Enzyme Activation MH - Fasting/metabolism MH - Gastric Mucosa/*metabolism/pathology MH - Gene Expression Regulation MH - Immunohistochemistry MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Nerve Tissue Proteins/genetics/*metabolism MH - Nucleobindins MH - Phosphorylation MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism MH - Tuberous Sclerosis Complex 1 Protein MH - Tuberous Sclerosis Complex 2 Protein MH - Tumor Suppressor Proteins/metabolism PMC - PMC3711577 EDAT- 2012/04/18 06:00 MHDA- 2012/08/10 06:00 PMCR- 2013/04/01 CRDT- 2012/04/18 06:00 PHST- 2012/01/16 00:00 [accepted] PHST- 2012/04/18 06:00 [entrez] PHST- 2012/04/18 06:00 [pubmed] PHST- 2012/08/10 06:00 [medline] PHST- 2013/04/01 00:00 [pmc-release] AID - 000338503 [pii] AID - cpb-0029-0493 [pii] AID - 10.1159/000338503 [doi] PST - ppublish SO - Cell Physiol Biochem. 2012;29(3-4):493-500. doi: 10.1159/000338503. Epub 2012 Apr 3.