Abstract
Obesity has emerged as an alarming health crisis due to its association with metabolic risk factors such as diabetes, dyslipidemia, and hypertension. Recent work has demonstrated the multifaceted roles of lncRNAs in regulating mouse adipose development, but their implication in human adipocytes remains largely unknown. Here we present a catalog of 3149 adipose active lncRNAs, of which 909 are specifically detected in brown adipose tissue (BAT) by performing deep RNA-seq on adult subcutaneous, omental white adipose tissue and fetal BATs. A total of 169 conserved human lncRNAs show positive correlation with their nearby mRNAs, and knockdown assay supports a role of lncRNAs in regulating their nearby mRNAs. The knockdown of one of those, lnc-dPrdm16, impairs brown adipocyte differentiation in vitro and a significant reduction of BAT-selective markers in in vivo. Together, our work provides a comprehensive human adipose catalog built from diverse fat depots and establishes a roadmap to facilitate the discovery of functional lncRNAs in adipocyte development.
Highlights
Obesity has emerged as an alarming health crisis due to its association with metabolic risk factors such as diabetes, dyslipidemia, and hypertension
Mammalian adipose tissue was historically classified as white adipose tissues (WATs) and brown adipose tissues (BAT)
Beige adipocytes show high phenotypic plasticity as they take on WAT morphology under basal state but show BAT-like morphology and thermogenic characteristics upon stimulation by cold exposure and agonists for β-adrenergic receptor or proliferator-activated receptor-γ (Ppar-γ)[6,7,8]
Summary
Obesity has emerged as an alarming health crisis due to its association with metabolic risk factors such as diabetes, dyslipidemia, and hypertension. Overexpression of HOTAIR in abdominal adipocytes led to increased percentage of differentiated cells and enhanced expression of adipogenic markers such as PPARγ27 Another recent work using human mesenchymal stem cells demonstrated the depletion of ADINR, a lncRNA transcribed divergently from Cebpα, resulted in impaired adipogenesis[28]. Our understanding of lncRNA in human adipocytes has been hindered by the lack of a comprehensive lncRNA catalog, in BAT due to the difficulty in sample collection Databases such as GENCODE or University of California at Santa Cruz (UCSC) represent some of the best reputable lncRNA depositories, but the current annotation (~15.9k, Gencode version 24) undermines the lncRNA population due to intrinsic low abundance and high tissue specificity[29]. Before the regulatory function of lncRNAs in human adipose and their therapeutic potential for obesity can be fully evaluated, it is needed to build a comprehensive human adipose lncRNA catalog
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