Sleep deprivation aggravates hepatocytes steatosis and insulin resistance by regulating exosomal microRNAs

Abstract Sleep deprivation (SD) threatens human health and increases the prevalence of disease with abnormal glycolipid metabolism, including metabolic dysfunction‐associated steatotic liver disease (MASLD) and insulin resistance (IR). However, the mechanism underlying SD induced MASLD and IR remains incompletely understood. Plasma samples were collected, and circulating exosomes were isolated. Differentially expressed miRNAs in exosomes were identified using an miRNA array and quantitative real‐time PCR (qPCR). MiRNA mimics or inhibitors were transfected into the cells to mimic the change in miRNA expression, and the biological effects of differentially expressed miRNAs were detected. Western blot and dual‐luciferase reporter assay were used to detect the specific target gene and molecular mechanism of miRNAs. Sleep deprived rats derived circulating exosomes strongly induced hepatic steatosis and IR. miRNA array combined with qPCR identified miR‐3572‐5p and miR‐183‐5p in exosomes that impacted abnormal glycolipid metabolism. Subsequently, miR‐3572‐5p inhibited fatty acid β‐oxidation by targeting PGC‐1α aggravated hepatic lipid accumulation. Meanwhile, both miR‐3572‐5p and miR‐183‐5p exerted an inhibitory effect on the PI3K/Protein Kinase B/GLUT4 insulin signaling pathway through distinct targeting of IRS1 and IGFBP7, which in turn contributed to the aggravation of IR. Notably, circulating exosomes enriched in miR‐3572‐5p were traced to peripheral blood monocytes, whereas those carrying miR‐183‐5p were pinpointed to adipose tissue. SD accelerates the progression of MASLD and IR by up‐regulating the expression of miR‐3572‐5p and down‐regulating the expression of miR‐183‐5p in circulating exosomes, thereby inhibiting fatty acid β‐oxidation and disrupting insulin signaling pathways.