Exosomal miRNA-714 derived from adipose tissue macrophages regulates adipocyte glucose and lipid metabolism via IGF1R targeting.

Abstract

Objective: This study aims to elucidate the regulatory role and underlying molecular mechanisms of exosomal microRNA (miR)-714, derived from adipose tissue macrophages (ATMs), in modulating glucose and lipid metabolism in adipocytes. The findings may contribute to the identification of novel therapeutic targets for obesity-related metabolic disorders.

Methods: Differentially expressed miRNAs and their corresponding target genes were identified through bioinformatics analyses using publicly available datasets. An obesity model was induced in mice via high-fat diet (HFD) administration to evaluate parameters such as body weight, blood glucose levels, and the expression of miR-714 and insulin-like growth factor 1 receptor (IGF1R) in ATM-derived exosomes. Cultured 3T3-L1 adipocytes were used for in vitro analyses. Target gene validation was conducted using dual-luciferase reporter assays. Glucose consumption, triglyceride (TG) content, and the expression of relevant metabolic genes were also measured.

Results: High-throughput analysis demonstrated a significant upregulation of miR-714 in ATM-derived exosomes from obese mice, accompanied by a downregulation of IGF1R expression in adipose tissue. In vivo findings confirmed elevated miR-714 levels in the HFD group, with a corresponding reduction in IGF1R protein levels. In vitro assays confirmed that the direct interaction between miR-714 and the 3' untranslated region (3'UTR) of Igf1r led to reduced Glucose consumption by adipocytes (reflected as increased glucose concentration in the culture supernatant), intracellular TG accumulation, and reduced IGF1R protein expression.

Conclusion: Exosomal miR-714 secreted by ATMs impairs Glucose consumption and promotes TG accumulation in adipocytes by downregulating IGF1R expression, thereby impairing Glucose consumption and promoting TG accumulation in adipocytes. These findings highlight the critical role of the miR-714/IGF1R axis in adipocyte metabolic regulation and provide a theoretical basis for non-invasive diagnostic strategies and targeted therapies for obesity-related metabolic conditions.