Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 29, Issue 3-4, Pages 493-500Publisher
KARGER
DOI: 10.1159/000338503
Keywords
Gastric mTOR; Gastric X/A like cells; Gastric hormones; Nesfatin-1/NUCB2
Categories
Funding
- National Natural Science Foundation of China [81030012, 30890043, 30971434, 30821001, 81170795, 30971085]
- Major National Basic Research Program of P. R. China [2010CB912504]
- Program for New Century Excellent Talents in University [NCET-10-0183]
- National Institute of Health [RO1DK043225]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK054032, R37DK043225, R01DK043225] Funding Source: NIH RePORTER
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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. Copyright (C) 2012 S. Karger AG, Basel
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