Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory of Research and Evaluation of Tissue Engineering Technology Products, School of Medicine, Nantong University, Nantong, China.
School of Life Sciences, Nantong University, Nantong, China.
EMBO Rep. 2023 Dec 6;24(12):e55467. doi: 10.15252/embr.202255467. Epub 2023 Oct 12.
Cold-induced nonshivering thermogenesis has contributed to the improvement of several metabolic syndromes caused by obesity. Several long noncoding RNAs (lncRNAs) have been shown to play a role in brown fat biogenesis and thermogenesis. Here we show that the lncRNA lnc266 is induced by cold exposure in inguinal white adipose tissue (iWAT). In vitro functional studies reveal that lnc266 promotes brown adipocyte differentiation and thermogenic gene expression. At room temperature, lnc266 has no effects on white fat browning and systemic energy consumption. However, in a cold environment, lnc266 promotes white fat browning and thermogenic gene expression in obese mice. Moreover, lnc266 increases core body temperature and reduces body weight gain. Mechanistically, lnc266 does not directly regulate Ucp1 expression. Instead, lnc266 sponges miR-16-1-3p and thus abolishes the repression of miR-16-1-3p on Ucp1 expression. As a result, lnc266 promotes preadipocyte differentiation toward brown-like adipocytes and stimulates thermogenic gene expression. Overall, lnc266 is a cold-inducible lncRNA in iWAT, with a key role in white fat browning and the thermogenic program.
冷诱导的非颤抖性产热有助于改善由肥胖引起的几种代谢综合征。已经有几种长链非编码 RNA（lncRNA）被证明在棕色脂肪生成和产热中发挥作用。在这里，我们表明 lncRNA lnc266 可被腹股沟白色脂肪组织（iWAT）中的冷暴露诱导。体外功能研究表明，lnc266 可促进棕色脂肪细胞分化和产热基因表达。在室温下，lnc266 对白色脂肪褐变和全身能量消耗没有影响。然而，在寒冷环境中，lnc266 可促进肥胖小鼠白色脂肪褐变和产热基因表达。此外，lnc266 可升高核心体温并减少体重增加。从机制上讲，lnc266 并不直接调节 Ucp1 的表达。相反，lnc266 可作为 miR-16-1-3p 的海绵，从而消除 miR-16-1-3p 对 Ucp1 表达的抑制作用。结果，lnc266 促进前脂肪细胞向棕色样脂肪细胞分化，并刺激产热基因表达。总的来说，lnc266 是 iWAT 中一种冷诱导的 lncRNA，在白色脂肪褐变和产热程序中起着关键作用。
