Identification of a Novel lncRNA in Gluteal Adipose Tissue and Evidence for Its Positive Effect on Preadipocyte Differentiation

Objective: Peripheral lower body fat is associated with lower cardiometabolic risk. Physiological differences in gluteal compared with abdominal subcutaneous (sc) adipocyte functions are known but the molecular basis for depot differences in adipocyte function is poorly understood. Our goal is to identify novel gene regulatory pathways that underlie the heterogeneity of human fat distribution. Methods: Abdominal and gluteal adipose tissue aspirates obtained from 35 subjects (age = 30 +/- 1.6 years; BMI = 27.3 +/- 1.3 kg/m(2)) 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. Results: A long noncoding RNA, HOTAIR that was expressed in gluteal but not in Abd sc adipose tissue was identified. 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 PPAR and LPL. Conclusions: HOTAIR 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 with abdominal adipocytes merits further study.