miR-184 Suppresses Adipocyte Lipogenesis by Targeting Hoxa5 and Downregulating the mTOR Pathway

FAN Yuwei^1,2, SHEN Ruili^1,2, XU Ke³, SHI Qiwen¹, ZHANG Jin^2,4*, WU Wenjing²*

（¹College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310000, China; ²College of Biological Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314001, China; ³Children’s Medical Center, the Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China; ⁴Jiaxing i-Bio Biotechnology Co., Ltd, Jiaxing 314050, China)

Abstract:

Adipocyte differentiation and lipid accumulation are tightly regulated processes, with miRNAs (microRNAs) playing a crucial role. This study investigates the function and mechanisms of miR-184 in lipid metabolism using miRNA-seq (miRNA sequencing) and functional cellular assays. miRNA-seq analysis of porcine IM (intramuscular) and SC (subcutaneous) adipocytes revealed significantly higher miR-184 expression in IM cells, which exhibit lower lipid accumulation, compared to SC cells with greater lipid storage capacity. Further analysis in 3T3-L1 mouse preadipocytes demonstrated a consistent decrease in miR-184 expression during differentiation, suggesting its role as a negative regulator of lipid accumulation. Overexpression of miR-184 via transfection with miR-184 mimics reduced intracellular triglyceride accumulation, suppressed the expression of lipogenic markers FAS (fatty acid synthase) and aP2 (fatty acid binding protein 4), and upregulated the lipolytic genes ATGL (adipose triglyceride lipase) and LPL (lipoprotein lipase). These effects were further confirmed using miR-184 inhibitors. Dual-luciferase reporter assays identified Hoxa5 as a direct target of miR-184, leading to suppression of mTOR signaling. In summary, miR-184 inhibits lipid accumulation in adipocytes by targeting Hoxa5 and downregulating the mTOR signaling pathway.

CSTR: 32200.14.cjcb.2025.07.0003