1. Academic Validation
  2. The Long Noncoding RNA ΒFaar Promotes White Adipose Tissue Browning and Prevents Diet-Induced Obesity

The Long Noncoding RNA ΒFaar Promotes White Adipose Tissue Browning and Prevents Diet-Induced Obesity

  • Adv Sci (Weinh). 2025 Jun 23:e05545. doi: 10.1002/advs.202505545.
Yue Yang 1 Bin Huang 1 Baixue Sha 1 Danni Gao 1 Yimeng Qin 1 Ziyi Li 1 Xi Chen 1 Yinuo Jin 2 Yi Pan 1 Yanfeng Zhang 1 Yumeng Shen 3 Yu Liu 4 Liang Jin 1 Fangfang Zhang 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, China.
  • 2 Nanjing HanKai Academy, Jiangpu Street, Pukou, Nanjing, Jiangsu Province, China.
  • 3 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
  • 4 Endocrinology Department, Sir Run Run Hospital of Nanjing Medical University, 109# Longmian Road, Nanjing, 210000, China.
Abstract

The conversion of white adipose tissue (WAT) to brown adipose tissue (BAT) is a promising strategy for obesity treatment. It is previously identified βFaar as a conserved long noncoding RNA (lncRNA) regulator of islet β-cell function in individuals with obesity, but its effect on WAT browning is not well understood. In this study, it is discovered that βFaar expression in adipose tissue markedly decreases with the progression of obesity in both mice and humans. βFaar in adipose tissue reduces lipid droplet (LD) size in WAT and promotes a browning phenotype in inguinal WAT (iWAT), leading to the amelioration of high-fat diet (HFD)-induced obesity. These effects can be attributed to crosstalk between βFaar and proteins within the master regulatory pathways of LD formation and WAT browning, including Ras oncogene family 18 (RAB18) and interferon regulatory factor 4 (IRF4). Specifically, βFaar inhibits LD swelling by binding to RAB18 and promoting IRF4 nuclear translocation, increases uncoupling protein 1 (UCP1) transcription, and further induces iWAT browning by binding to karyopherin subunit alpha 6 (KPNA6). Together, these results demonstrate the critical roles of βFaar in regulating iWAT browning and preserving metabolic health; thus, βFaar may be a potential therapeutic target for management of obesity and related disorders.

Keywords

browning; lipid droplets; lncRNA; obesity; white adipose tissue.

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