Int J Biol Sci 2021; 17(5):1302-1314. doi:10.7150/ijbs.56477
Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation
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.
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. Available from https://www.ijbs.com/v17p1302.htm
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