Location: Children's Nutrition Research CenterTitle: SIRT1 regulates the mouse gastric emptying and intestinal growth Author
Submitted to: Gastroenterology
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2010
Publication Date: 5/1/2010
Citation: Guan, X., Wang, Y., Qi, J., Shi, X., Li, X., Uray, K.S., Guo, Y., Li, D., Xia, B., Burrin, D. 2010. SIRT1 regulates the mouse gastric emptying and intestinal growth [abstract]. Gastroenterology. 138(5):S-402. Interpretive Summary:
Technical Abstract: This study addressed physiological significance of SIRT1 gene on mouse gastrointestinal growth and function (gastric emptying and intestinal growth). SIRT1 (a NAD+-dependent histone deacetylase) is a key cellular energy sensor, and involved in a wide variety of cellular functions including energy metabolism, cell cycle, and immune response. However, it is unknown whether SIRT1 regulates the mouse gastric emptying and intestinal growth in response to intake of food. In this experiment, 40 10-week-old SIRT1 knockout (KO) and wild-type (WT) mice were fasted 24 h or refed 1 h to define its physiological function. Our results showed: 1). SIRT1 protein was localized to mucosal epithelial nuclei using confocal immunohistochemistry. The abundance of the SIRT1protein in the gut was increased during fast, but undetectable during refeeding. 2) The KO mice showed increased jejunal villous length, enhanced crypt proliferation (indicated by increased percentage of BrdU–labeled cells), but suppressed mucosal apoptosis (indicated by decreased abundance of cleaved caspase 3 protein) when compared with their WT littermates during fast. Notably, this phenotype was associated with decreased abundance of p53 protein and increased translocalization of Beta-catenin to the nucleus from cytoplasm and membrane in the gut. 3). When compared with their WT littermates, the KO mice under stress-free, conscious condition shows accelerated gastric emptying using 13C-octanoic acid breath test. Moreover, the ex vivo spontaneous contraction (i.e., basal activity) of the KO mouse small intestine was increased using chamber technique. We conclude that SIRT1 plays a critical role in regulating intestinal epithelial homeostasis (cell proliferation and death) and gastrointestinal motility, suggesting a novel mechanism of SIRT1 activation required for energy reserve in the body.