MiRNA array of hepatic extracellular vesicles in Ggpps-LKO mice

Lipid overload results in lipid redistribution among metabolic organs such as liver, adipose, and muscle; therefore, the interplay between liver and other organs is important to maintain lipid homeostasis. Here, we show that liver responds to lipid overload firstly and sends hepatocyte-derived extracellular vesicles (EVs) targeting adipocytes to regulate adipogenesis and lipogenesis. Geranylgeranyl diphosphate synthase (Ggpps) expression in liver is enhanced by lipid overload and regulates EV secretion through Rab27A geranylgeranylation. Consistently, liver-specific Ggpps deficiency mice have reduced fat adipose deposition. The levels of several EV-derived miRNAs in the plasma of nonalcoholic fatty liver disease (NAFLD) patients are positively correlated with body mass index (BMI), and these miRNAs enhance adipocyte lipid accumulation. Thus, we highlight an inter-organ mechanism whereby the liver senses different metabolic states and sends corresponding signals to remodel adipose tissue to adapt to metabolic changes in response to lipid overload. The miRNA components in primary hepatocyte-derived EVs from WT and liver Ggpps defficient mice fed a normal chow diet or a HFD were profiled. Each sample comprised a pool of EVs derived from the primary hepatocytes of four animals.