The release of exosomes from adipose tissue macrophages (ATMs), hepatocytes and islet β-cells have systemic metabolic effects. Exosomal miRNA (miR)-690 from M2-like ATMs improves insulin sensitivity, while miR-155 from M1-like ATMs can cause insulin resistance. In early stage HFD, hepatocytes secrete exosomes containing miR-3075, which produces beneficial metabolic effects. In contrast, the hepatocyte exosomes in chronically obese mice contain miR-434-5p, which promotes inflammation and insulin resistance. Exosomes from steatotic hepatocytes also contain pathogenic miRs, such as miR-128 and miR-1, that can induce inflammation or cause hepatic stellate cell activation, promoting NASH. β-cells stressed by pro-inflammatory stimuli release exosomes containing miR-21-5p, which can induce apoptosis in neighboring β-cells.