Linc-ADAIN, A Human Adipose LincRNA Regulates Adipogenesis by Modulating KLF5 and IL-8 mRNA stability

Adipose tissue remodeling and dysfunction, characterized by increased inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2DM) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here we describe the functions of linc-ADAIN (ADipose Anti-INflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans. We demonstrate that linc-ADAIN knockdown (KD) increases KLF5 and IL-8 mRNA stability and translation, by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, led to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo, KD of linc-ADAIN in human ASC hTERT adipocytes implanted into mice, increased adipocyte size and macrophage infiltration compared to implanted control adipocytes, mimicking hallmark features of obesity-induced adipose tissue remodeling. Linc-ADAIN is an anti-inflammatory lincRNA that limits adipose tissue expansion and lipid storage. Overall design: Confluent primary ASC52telo hTERTs were transfected with Scramble shRNA or linc-ADAIN shRNA. Then after 2 days adipocyte differentiation media was added for 7 days, then maintenance media for 7 days (Day 14). On Day 14, LPS (100 ng/mL) was added for 4 hours. 3 replicates were used for each combination of Scramble/linc-ADAIN shRNA and +/- LPS. RNA was extracted and submitted to sequencing.