title: Regulation of gastric nesfatin-1/NUCB2.
abstract: Originally identified in the hypothalamus as a satiety factor, recent studies provide evidence that nefatin-1/NUCB2 is a gutbrain peptide with a broader array of actions. Detection of abundant nesfatin-1/NUCB2 in gastric X/A like endocrine cells, which also produce the orexigenic hormone ghrelin, indicates that gastric mucosa may be one of the predominant sources of nesfatin-1/NUCB2. Functional studies have revealed significant effects of nefatin-1 on inhibition of feeding behavior and on glucose homeostasis. These metabolic functions make nesfatin-1/NUCB2 a novel candidate for treatment of obesity and diabetes. However, deficiencies in our understanding of nesfatin-1/NUCB2 receptor pose a significant hurdle for therapies that target its action. Defining novel pathways to alter the production of nesfatin-1/NUCB2 would shift therapeutic focus to gastric targets. A necessary precondition is improved understanding of the mechanisms by which nesfatin-1/NUCB2 is synthesized and secreted by gastric X/A like cells. Recent studies provide evidence that mTOR is a critical regulatory molecule in these endocrine cells and that its activity is linked to the production of ghrelin and nesfatin- 1/NUCB2. These findings suggest that gastric mTOR is involved in the regulation of food intake and overall energy metabolism through modulation of ghrelin and nesfatin-1/NUCB2. In this review, we first summarize current advances in the relationship between organism energy status and nesfatin-1/NUCB2 levels, and then discuss the novel finding on mTOR as the gastric fuel sensor and its role in the regulation of nesfatin-1/NUCB2 expression.
authors.affiliation: Department of Surgery, the University of Michigan Medical Center, 4618B, MS II, 1150 W. Medical Center Dr., Ann Arbor, MI 48109, USA. weizhenz@umich.edu.
authors.forename: Ziru
authors.initials: Z
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Mulholland
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D002135:Calcium-Binding Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000502:physiology*; D000080866:Nucleobindins; D009765:Obesity / Q000628:therapy; D013270:Stomach / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D058570:TOR Serine-Threonine Kinases