Int J Biol Sci 2021; 17(5):1302-1314. doi:10.7150/ijbs.56477 This issue Cite

Research Paper

Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation

Na Sun1,2*, Fandong Meng3*, Jie Zhao1,2, Xueqin Li1,2, Rongqing Li1,2, Jing Han1,2, Xin Chen1,2, Wanpeng Cheng1,2, Xiaoying Yang1,2, Yanbo Kou1,2, Kuiyang Zheng1,2,4✉, Jing Yang1,2,4✉, Takayuki Ikezoe5

1. Jiangsu Province Key Laboratory of Immunity and Metabolism, Affiliated Hospital of Xuzhou Medical University.
2. Department of Pathogenic Biology and Immunology, Affiliated Hospital of Xuzhou Medical University.
3. Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University.
4. National Experimental Demonstration Center for Basic Medicine Education, Xuzhou Medical University, Xuzhou, Jiangsu, China.
5. The Department of Hematology, Fukushima Medical University, Fukushima, Japan.
*These authors contributed equally to this work.

Citation:
Sun N, Meng F, Zhao J, Li X, Li R, Han J, Chen X, Cheng W, Yang X, Kou Y, Zheng K, Yang J, Ikezoe T. Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation. Int J Biol Sci 2021; 17(5):1302-1314. doi:10.7150/ijbs.56477. https://www.ijbs.com/v17p1302.htm
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Abstract

Graphic abstract

Aurora-A kinase, a serine/threonine mitotic kinase involved in mitosis, is overexpressed in several human cancers. A recent study showed that Aurora-A mediates glucose metabolism via SOX8/FOXK1 in ovarian cancer. However, the roles of Aurora-A in metabolic diseases remain unclear. This study found that Aurka loss in the intestinal epithelium promoted age-induced obesity and enlargement of lipid droplets in parallel with an increase in infiltrated macrophages in the white adipocyte tissue (WAT) of male mice. Moreover, loss of Aurka induced the expression of lipid metabolism regulatory genes, including acetyl-coenzyme A carboxylase 1 (Acc1), in association with an increase in the levels of p-AKT in the intestinal epithelium as well as WAT. Blockade of AKT activation reduced the expression of lipid metabolism regulatory genes. In subsequent experiments, we found that the Firmicutes abundance and the levels of short-chain fatty acids (SCFAs) in the gut were dramatically increased in Aurkaf/+;VillinCre/+ mice compared with Aurkaf/+ mice. Additionally, propionate increased the phosphorylation of AKT in vitro. These observations indicated that Aurka loss in the intestinal epithelium contributed to gut microbiota dysbiosis and higher levels of SCFAs, especially propionate, leading to AKT activation and lipid metabolism regulatory gene expression, which in turn promoted age-induced obesity.

Keywords: Aurora-A, AKT, obesity, IL-6


Citation styles

APA
Sun, N., Meng, F., Zhao, J., Li, X., Li, R., Han, J., Chen, X., Cheng, W., Yang, X., Kou, Y., Zheng, K., Yang, J., Ikezoe, T. (2021). Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation. International Journal of Biological Sciences, 17(5), 1302-1314. https://doi.org/10.7150/ijbs.56477.

ACS
Sun, N.; Meng, F.; Zhao, J.; Li, X.; Li, R.; Han, J.; Chen, X.; Cheng, W.; Yang, X.; Kou, Y.; Zheng, K.; Yang, J.; Ikezoe, T. Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation. Int. J. Biol. Sci. 2021, 17 (5), 1302-1314. DOI: 10.7150/ijbs.56477.

NLM
Sun N, Meng F, Zhao J, Li X, Li R, Han J, Chen X, Cheng W, Yang X, Kou Y, Zheng K, Yang J, Ikezoe T. Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation. Int J Biol Sci 2021; 17(5):1302-1314. doi:10.7150/ijbs.56477. https://www.ijbs.com/v17p1302.htm

CSE
Sun N, Meng F, Zhao J, Li X, Li R, Han J, Chen X, Cheng W, Yang X, Kou Y, Zheng K, Yang J, Ikezoe T. 2021. Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation. Int J Biol Sci. 17(5):1302-1314.

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