SLC7A14 imports GABA to lysosomes and impairs hepatic insulin sensitivity via inhibiting mTORC2

• DOI: 10.1016/j.celrep.2022.111984
• Publication Date: 2023-01-10T19:12:00Z
• Authors: Xiaoxue Jiang; Kan Liu; Haizhou Jiang; Hanrui Yin; En-duo Wang; Hong Cheng; Feixiang Yuan; Fei Xiao; Fenfen Wang; Wei Lu; Bo Peng; Yousheng Shu; Xiaoying Li; Shanghai Chen; Feifan Guo
• Keywords: mTORC2

Lysosomal amino acid accumulation is implicated in several diseases, but its role insulin resistance, the central mechanism to type 2 diabetes and many metabolic unclear. In this study, we show hepatic expression of lysosomal membrane protein solute carrier family 7 member 14 (SLC7A14) increased insulin-resistant mice. The promoting effect SLC7A14 on resistance demonstrated by loss- gain-of-function experiments. further as a transporter resulting γ-aminobutyric (GABA), which induces via inhibiting mTOR complex (mTORC2)'s activity. These results establish causal link between acids suggest that inhibition may provide therapeutic strategy treating resistance-related GABA-related diseases insights into upstream mechanisms for mTORC2, master regulator important processes.