Liver-Derived Exosomes Induce Inflammation and Lipogenesis in Mice Fed High-Energy Diets.

ABSTRACT

The liver is an endocrine organ and is the first organ exposed to nutrients when they are absorbed into the body before being metabolized by the distal organs. Although the liver plays an essential role in the interactions between the metabolic organs, their regulatory mechanisms have not been elucidated. Exosomes mediate communication between cells and primarily enable the transport of lipids, mRNAs, miRNAs, and proteins between cells. In this study, we investigated the effects of lipid metabolism on the liver and adipose tissue between mice fed high-fat (HF) and high-fat/sucrose (HFS) diets and determined the effects of liver tissue-derived exosomes on adipocytes to understand the underlying mechanisms associated with obesity-related metabolic diseases. Normal, HF, and HFS diets were fed to the mice for 12 weeks to compare differences based on dietary patterns. We showed different lipid metabolism effects on the liver and adipose tissue between HF- and HFS-fed mice. In the liver, fibrosis, inflammation, and lipogenesis were activated at higher levels in the HFS than in the HF group, and lipolysis was activated at higher levels in the HF than in the HFS group. In adipose tissue, adipogenesis, fatty acid transport, and lipolysis were activated at higher levels in the HF than in the HFS group, and inflammation and lipogenesis were activated at higher levels in the HFS than in the HF group. This result followed a similar trend reported in 3T3-L1 cells treated with liver-derived exosomes. In addition, the TG content of the liver-derived exosomes was significantly higher, and lipid accumulation was accelerated in the HFS than in the HF group. Based on these results, continuous exposure to HF and HFS diets induces lipid accumulation mediated by liver-derived exosomes; however, there is a difference in lipid metabolism. These results contribute to the elucidation of the mechanisms of exosome function in relation to obesity-related metabolic diseases and the metabolic relationship between tissues.