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

IF 14.3 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Yue Yang, Bin Huang, Baixue Sha, Danni Gao, Yimeng Qin, Ziyi Li, Xi Chen, Yinuo Jin, Yi Pan, Yanfeng Zhang, Yumeng Shen, Yu Liu, Liang Jin, Fangfang Zhang
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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.

长链非编码RNA ΒFaar促进白色脂肪组织褐变,防止饮食引起的肥胖。
白色脂肪组织(WAT)转化为棕色脂肪组织(BAT)是一种很有前途的肥胖治疗策略。先前已确定βFaar是肥胖个体胰岛β细胞功能的保守长链非编码RNA (lncRNA)调节剂,但其对WAT褐变的影响尚不清楚。在本研究中,我们发现βFaar在脂肪组织中的表达随着小鼠和人类肥胖的进展而显著降低。脂肪组织中的βFaar降低WAT中的脂滴(LD)大小,促进腹股沟WAT (iWAT)中的褐变表型,从而改善高脂肪饮食(HFD)诱导的肥胖。这些作用可归因于βFaar与LD形成和WAT褐变主要调控通路中的蛋白之间的串扰,包括RAS癌基因家族18 (RAB18)和干扰素调节因子4 (IRF4)。具体而言,βFaar通过与RAB18结合,促进IRF4核易位,抑制LD肿胀,增加解偶联蛋白1 (UCP1)转录,并通过与核丝蛋白亚单位α 6 (KPNA6)结合,进一步诱导iWAT褐变。总之,这些结果表明βFaar在调节iWAT褐变和保持代谢健康中的关键作用;因此,βFaar可能是管理肥胖和相关疾病的潜在治疗靶点。
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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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