Identification of a novel lncRNA in gluteal adipose tissue and evidence for its positive effect on preadipocyte differentiation

Abstract

ContextPeripheral lower body fat is associated with lower cardiometabolic risk. Physiological differences in gluteal compared to abdominal subcutaneous (sc) adipocyte functions are known but the molecular basis for depot differences in adipocyte function is poorly understood.ObjectiveTo identify novel gene regulatory pathways that underlie the heterogeneity of human fat distribution.Design and methodsAbdominal and gluteal adipose tissue aspirates obtained from 35 subjects (age=30±1.6 years; BMI=27.3±1.3kg/m2) were analyzed using Illumina microarrays and confirmed by RT-PCR. The HOTAIR gene was stably transfected into primary cultured human abdominal sc preadipocytes using a lentivirus and effects on adipogenic differentiation were analyzed.ResultsWe identified a long non-coding RNA, HOTAIR that was expressed in gluteal but not in Abd sc adipose tissue. This difference was retained throughout in vitro differentiation and was maximal at day 4. Ectopic expression of HOTAIR in abdominal preadipocytes produced an increase in differentiation as reflected by a higher percentage of differentiated cells, and increased expression of key adipogenic genes including PPARγ and LPL.ConclusionHOTAIR is expressed in gluteal adipose and may regulate key processes in adipocyte differentiation. The role of this lncRNA in determining the metabolic properties of gluteal compared to abdominal adipocytes merits further study.

Long noncoding RNAs in regulating adipogenesis: new RNAs shed lights on obesity

“…In addition, lncRNAs tend to be expressed at lower levels compared with mRNAs [29–31], and a high proportion of lncRNAs are preferentially expressed in specific tissues or cell lines [30, 32]. The expression of adipose lncRNAs is low and depot-specific [33, 34]. According to its position with respect to protein coding genes, a lncRNA can be classified into one or more of five categories [21]: sense, antisense, bidirectional, intronic, and intergenic (Fig.…”

“…Recently, a study has shown that HOTAIR participated in human subcutaneous preadipocyte differentiation [34]. HOTAIR was expressed in human gluteal fat but not in abdominal subcutaneous adipose tissue, and HOTAIR expression increased by twofold during gluteal preadipocyte differentiation in vitro [34].…”

“…Recently, a study has shown that HOTAIR participated in human subcutaneous preadipocyte differentiation [34]. HOTAIR was expressed in human gluteal fat but not in abdominal subcutaneous adipose tissue, and HOTAIR expression increased by twofold during gluteal preadipocyte differentiation in vitro [34]. Ectopic expression of HOTAIR in abdominal preadipocytes enhanced the percentage of differentiated cells and increased expressions of functional adipogenic markers including PPARγ, LPL (lipoprotein lipase), FABP4, and AdipoQ, with no effect on preadipocyte proliferation rate [34], suggesting an underlying transcriptional mechanism for HOTAIR to modulate preadipocyte differentiation.…”

“…Nevertheless, the role of SRA on obesity and the metabolic syndrome deserves further attention. Followed to SRA, lnc-RAP-n, slincRAD, PU.1 AS, HOTAIR, ADINR, and NEAT1 are also found to be involved in white preadipocyte differentiation [13, 34, 42, 45, 46, 50]. Furthermore, Blnc1 and lnc-BATE-1 positively regulate brown or beige adipogenesis via forming a ribonucleoprotein complex with distinct transcriptional factors [33, 51].…”

Transcriptome Profile Analysis Reveals an Estrogen Induced LncRNA Associated with Lipid Metabolism and Carcass Traits in Chickens (Gallus Gallus)

“…Many studies have suggested that lncRNAs serve as important controllers during adipogenesis [6], adipocyte differentiation [7], liver development [8], and hepatic lipid metabolism [9]. Some lncRNAs play an important role in the cholesterol metabolism in HepG2 cells [10].…”