Adiponectin AS lncRNA inhibits adipogenesis by transferring from nucleus to cytoplasm and attenuating Adiponectin mRNA translation

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. Proposed mechanism by which AdipoQ AS lncRNA inhibits adipogenesis. A) In vitro effect and molecular mechanism of AdipoQ AS lncRNA. AdipoQ AS lncRNA transfers from nucleus to cytoplasm, inhibiting adipogenic differentiation through forming a sense/antisense RNA duplex to prevent translation of AdipoQ mRNA. B) In vivo effect of AdipoQ AS lncRNA. AdipoQ AS lncRNA and NOR decrease the WAT, BAT and liver TG in HFD mice, but NOR improves the GTT and ITT. [Display omitted] •AdipoQ AS lncRNA transcribed from AdipoQ opposite strand is more stable than its mRNA.•AdipoQ AS lncRNA transfers from nucleus to cytoplasm during adipogenesis.•AdipoQ AS lncRNA inhibits lipogenesis by forming an RNA duplex with its mRNA.•AdipoQ AS lncRNA decreases WAT, BAT and liver TG in HFD mice.•Non-overlapping region of AdipoQ AS lncRNA improves GTT and ITT in HFD mice.