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.
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 obesemice, 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 obesemice. 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.
Authors: H Shimizu; S Oh-I; K Hashimoto; M Nakata; S Yamamoto; N Yoshida; H Eguchi; I Kato; K Inoue; T Satoh; S Okada; M Yamada; T Yada; M Mori Journal: Endocrinology Date: 2008-10-16 Impact factor: 4.736
Authors: Andreas Stengel; Miriam Goebel; Iskandar Yakubov; Lixin Wang; Derrick Witcher; Tamer Coskun; Yvette Taché; George Sachs; Nils W G Lambrecht Journal: Endocrinology Date: 2008-09-25 Impact factor: 4.736
Authors: Sung Hee Um; Francesca Frigerio; Mitsuhiro Watanabe; Frédéric Picard; Manel Joaquin; Melanie Sticker; Stefano Fumagalli; Peter R Allegrini; Sara C Kozma; Johan Auwerx; George Thomas Journal: Nature Date: 2004-08-11 Impact factor: 49.962
Authors: Andreas Stengel; Miriam Goebel; Lixin Wang; Jean Rivier; Peter Kobelt; Hubert Mönnikes; Nils W G Lambrecht; Yvette Taché Journal: Endocrinology Date: 2009-10-01 Impact factor: 4.736
Authors: James Brugarolas; Kui Lei; Rebecca L Hurley; Brendan D Manning; Jan H Reiling; Ernst Hafen; Lee A Witters; Leif W Ellisen; William G Kaelin Journal: Genes Dev Date: 2004-11-15 Impact factor: 11.361