When LXA4 meets white fat: browning via the miR-133a-3p/SIRT1 pathway in mouse models

Given the established positive role of Lipoxin A4 (LXA4) in adipose browning at the cellular level, this study investigated its possible effect on white fat browning and the underlying molecular mechanisms. The obese insulin resistance mouse model was established. The body weight, subcutaneous and visceral fat, and food intake of the mice were observed. Haematoxylin-eosin staining was used to determine the effects of LXA4 on the morphology of inguinal white adipose tissue and brown adipose tissue, and to analyse the changes in fat mass and serum insulin levels, lipid metabolism and other indexes. The cellular experiments included the induction of browning in 3T3-L1 precursor adipocytes, the screening of miRNAs related to adipose browning and their downstream target genes using TargetScan, qRT-PCR, RNA immunoprecipitation and dual luciferase reporter assay. LXA4 attenuated weight gain, inhibited fat accumulation, and improved hyperlipidaemia and insulin resistance in high-fat diet-treated mice. LXA4 also promoted browning of 3T3-L1 precursor adipocytes. Activation of miR-133a-3p partially abrogated LXA4-induced promotion of white adipose browning. The effects of LXA4 and miR-133a-3p could be reversed by SIRT1. Collectively, LXA4 alleviates obesity-related metabolic disorders by promoting inguinal white adipose browning and improving insulin resistance possibly through the miR-133a-3p/SIRT1 pathway.