SLC7A11 and mGluR5 identified as targets for hepatic alcoholic steatosis

INDICATION: Liver disease

Inhibiting SLC7A11, which excretes glutamate from cells, or the glutamate receptor mGluR5 could treat alcoholic steatosis of the liver. Patients with alcoholic fatty liver disease had elevated plasma levels of glutamate and liver levels of SLC7A11 mRNA and protein and mGluR5 mRNA. In mice with alcoholic steatosis, hepatocyte-specific SLC7A11 knockout or treatment with the SLC7A11 inhibitor Azulfidine sulfasalazine or an adeno-associated viral (AAV) vector encoding an shRNA against SLC7A11 reduced serum glutamate levels and liver accumulation of fat. Also in mice, systemic or hepatic stellate cell-specific knockout of mGluR5 or administration of an mGluR5 inhibitor tool compound decreased hepatic fat accumulation...