Research ArticleMetabolism

Interrogation of nonconserved human adipose lincRNAs identifies a regulatory role of linc-ADAL in adipocyte metabolism

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Science Translational Medicine  20 Jun 2018:
Vol. 10, Issue 446, eaar5987
DOI: 10.1126/scitranslmed.aar5987

A possible linc to obesity

Both noncoding and evolutionarily nonconserved RNAs were long presumed to be nonfunctional but are increasingly reported to have biological roles. Here, Zhang et al. identified hundreds of putative long intergenic noncoding RNAs (lincRNAs) in human gluteal subcutaneous adipose tissue. Some of the nonconserved lincRNAs associated with active histone marks and transcription factor binding or were modulated by bariatric surgery–induced weight loss. The authors showed how one nonconserved lincRNA, linc-ADAL, helps regulate adipocyte differentiation and de novo lipogenesis by interacting with distinct nucleic and cytoplasmic factors. Further studies will be needed to show whether linc-ADAL could be a therapeutic target in obesity or other metabolic conditions.


Long intergenic noncoding RNAs (lincRNAs) have emerged as important modulators of cellular functions. Most lincRNAs are not conserved among mammals, raising the fundamental question of whether nonconserved adipose-expressed lincRNAs are functional. To address this, we performed deep RNA sequencing of gluteal subcutaneous adipose tissue from 25 healthy humans. We identified 1001 putative lincRNAs expressed in all samples through de novo reconstruction of noncoding transcriptomes and integration with existing lincRNA annotations. One hundred twenty lincRNAs had adipose-enriched expression, and 54 of these exhibited peroxisome proliferator–activated receptor γ (PPARγ) or CCAAT/enhancer binding protein α (C/EBPα) binding at their loci. Most of these adipose-enriched lincRNAs (~85%) were not conserved in mice, yet on average, they showed degrees of expression and binding of PPARγ and C/EBPα similar to those displayed by conserved lincRNAs. Most adipose lincRNAs differentially expressed (n = 53) in patients after bariatric surgery were nonconserved. The most abundant adipose-enriched lincRNA in our subcutaneous adipose data set, linc-ADAL, was nonconserved, up-regulated in adipose depots of obese individuals, and markedly induced during in vitro human adipocyte differentiation. We demonstrated that linc-ADAL interacts with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis.

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