ABSTRACT The role of m 6 A RNA methylation in obstructive sleep apnea (OSA)‐related metabolic dysfunction and systemic inflammation is unknown. We aimed to identify the key m 6 A regulator involved in OSA‐induced adipose tissue inflammation and explore the underlying mechanisms. The expression of m 6 A methylation regulators was measured and their associations with systemic inflammation indicators were analyzed in patients with OSA. A mouse model of OSA was established with high‐fat diet feeding and chronic intermittent hypoxia (CIH) treatment. The histological alterations of epididymal white adipose tissue (eWAT) were evaluated. The effects and mechanisms of methyltransferase‐like 14 (METTL14) on regulating macrophage polarization were determined by in vitro assays. The global m 6 A RNA methylation levels and the expression levels of m 6 A methylation regulators were altered in OSA patients. The mRNA expression level of METTL14 was negatively associated with systemic inflammation parameters. CIH treatment aggravated the infiltration of macrophages in the eWAT of mice. The mRNA and protein levels of METTL14 were downregulated in the eWAT of mice treated with CIH and in hypoxia‐treated THP‐1 macrophages. Overexpression of METTL14 was able to inhibit hypoxia‐induced M1 macrophage polarization and restore the M1/M2 balance. Mechanistically, METTL14 overexpression mediated JAK2 m 6 A RNA methylation and promoted the decay of JAK2 mRNA, leading to the inhibition of the JAK2/STAT3 signaling pathway. These findings suggest an important role of METTL14 in regulating adipose tissue dysfunction and metabolic inflammation caused by OSA. Modulating m 6 A RNA methylation of the JAK2/STAT3 signaling pathway has therapeutic potential for OSA‐related metabolic disorders and systemic inflammation.
Zhang et al. (Tue,) studied this question.