Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Apr;1863(4):420-432. doi: 10.1016/j.bbalip.2018.01.005.
Adiponectin (AdipoQ) is an adipocyte-derived hormone with positive function on systemic glucose and lipid metabolism. Long noncoding RNA (lncRNA) is emerging as a vital regulator of adipogenesis. However, AdipoQ-related lncRNAs in lipid metabolism have not been explored. Here, AdipoQ antisense (AS) lncRNA was first identified, and we further found that it inhibited adipogenesis. The half-life of AdipoQ AS lncRNA was 10 h, whereas that of AdipoQ mRNA was 4 h. During adipogenic differentiation, AdipoQ AS lncRNA translocated from nucleus to cytoplasm. AdipoQ AS lncRNA and AdipoQ mRNA formed an RNA duplex. Moreover, AdipoQ AS lncRNA delivered via injection of adenovirus expressing AdipoQ AS lncRNA decreases white adipose tissue (WAT), brown adipose tissue (BAT) and liver triglycerides (TG) in mice consuming a high fat diet (HFD). Interestingly, the non-overlapping region of AdipoQ AS lncRNA improved serum glucose tolerance and insulin sensitivity in HFD mice, but not AdipoQ AS lncRNA. In conclusion, AdipoQ AS lncRNA transfer from nucleus to cytoplasm inhibits adipogenesis through formation of an AdipoQ AS lncRNA/AdipoQ mRNA duplex to suppress the translation of AdipoQ mRNA. Taken together, we suggest that AdipoQ AS lncRNA is a novel therapeutic target for obesity-related metabolic diseases.
脂联素 (AdipoQ) 是一种脂肪细胞衍生的激素，对全身葡萄糖和脂质代谢具有积极作用。长链非编码 RNA (lncRNA) 正成为脂肪生成的重要调节因子。然而，脂质代谢中与 AdipoQ 相关的 lncRNA 尚未被探索。在这里，首次鉴定了 AdipoQ 反义 (AS) lncRNA，我们进一步发现它抑制了脂肪生成。AdipoQ AS lncRNA 的半衰期为 10 小时，而 AdipoQ mRNA 的半衰期为 4 小时。在脂肪生成分化过程中，AdipoQ AS lncRNA 从细胞核转位到细胞质。AdipoQ AS lncRNA 和 AdipoQ mRNA 形成 RNA 双链。此外，通过注射表达 AdipoQ AS lncRNA 的腺病毒传递 AdipoQ AS lncRNA 可减少高脂肪饮食 (HFD) 小鼠的白色脂肪组织 (WAT)、棕色脂肪组织 (BAT) 和肝脏甘油三酯 (TG)。有趣的是，AdipoQ AS lncRNA 的非重叠区域改善了 HFD 小鼠的血清葡萄糖耐量和胰岛素敏感性，但 AdipoQ AS lncRNA 没有。总之，AdipoQ AS lncRNA 从细胞核到细胞质的转移通过形成 AdipoQ AS lncRNA/AdipoQ mRNA 双链来抑制脂肪生成，从而抑制 AdipoQ mRNA 的翻译。综上所述，我们认为 AdipoQ AS lncRNA 是肥胖相关代谢性疾病的一种新的治疗靶点。
