Zhaojin Liu (University of Wisconsin-Madison)| Lucas O'Neill (University of Wisconsin-Madison)| James Ntambi (University of Wisconsin-Madison, University of Wisconsin-Madison)
Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-limiting step in the biosynthesis of monounsaturated acids. Hepatic deletion of Scd1 protects mice from high-carbohydrate diet-induced hepatic steatosis and adiposity in part by suppressing hepatic lipogenesis, increasing adipose tissue lipogenesis, and increasing systemic glucose uptake. However, the mechanism leading to these phenotypes is unclear. Deletion of Scd1 in cultured AML12 hepatocytes does not recapitulate decreased lipogenic gene expression, which indicates that an extrahepatic messenger is required. In mice lacking hepatic Scd1, expression of adiponectin (AdipoQ), an adipokine, is significantly elevated in the adipose tissue and blood. Therefore, we hypothesized that crosstalk between liver and adipose tissue is required to suppress hepatic lipogenesis and that adipose tissue-derived ADIPOQ is the messenger. Here we show, that co-culturing Scd1 deficient AML12 hepatocytes with fully differentiated 3T3-L1 adipocytes, induces the expression of AdipoQ, fatty acid synthase (Fasn), and carbohydrate response element-binding protein (ChREBP) in the adipocyte fraction and suppresses the lipogenic genes, sterol regulatory element-binding protein-1c (Srebp1c) and Fasn in the hepatocyte fraction. Furthermore, we show that treating HepG2 cells with ADIPOQ suppresses the lipogenic genes SREBP1c, FASN, and ChREBP compared to control cells. In conclusion, our results suggest that liver-adipose crosstalk mediates hepatic lipogenic gene expression in mice lacking hepatic Scd1.