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Adiponectin AS lncRNA inhibits adipogenesis by transferring from nucleus to cytoplasm and attenuating Adiponectin mRNA translation
Authors:Rui Cai  Yunmei Sun  Naren Qimuge  Guoqiang Wang  Yingqian Wang  Guiyan Chu  Taiyong Yu  Gongshe Yang  Weijun Pang
Affiliation:Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China
Abstract: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.
Keywords:AdipoQ  Adiponectin  AS lncRNA  antisense long noncoding RNA  FISH  RPA  ribonuclease protection assay  iWAT  inguinal white adipose tissue  eWAT  epididymal white adipose tissue  BAT  brown adipose tissue  TG  triglyceride  HFD  high fat diet  RNA-Seq  RNA sequencing  FFAs  free fatty acids  GTT  glucose tolerance test  ITT  insulin tolerance test  CPC  Coding Potential Calculator  CPAT  Coding Potential Assessment Tool  NOR  Ad-AS  Ad-NOR  adenovirus expressing NOR  insulin receptor  insulin receptor substrate  peroxisome proliferator activated receptor γ  CCAAT/enhancer binding protein α  fatty acid binding protein 4  carnitine palmitoyl transferase 1 α  hormone sensitive lipase  adipose triglyceride lipase  sterol responsible element binding protein 1c  tumor necrosis factor α  uncoupling protein 1  peroxisome proliferator activated receptor gamma coactivator-1 alpha  PRD1-BF1-RIZ1 homologous domain-containing protein 16  FISH  Half-life  Adipogenesis  RNA duplex  Lipid metabolism
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