linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability

Adipose tissue remodeling and dysfunction, characterized by elevated inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2D) 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 interleukin-8 (IL-8) mRNA stability and translation by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, leads to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo. KD of linc-ADAIN in human adipose stromal cell (ASC) hTERT adipocytes implanted into mice increases 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. [Display omitted] •linc-ADAIN expression increases during adipocyte differentiation•linc-ADAIN is suppressed in white adipose tissue of obese humans•Knockdown of linc-ADAIN leads to increased inflammation and sustained adipogenesis•linc-ADAIN knockdown increases IL-8 and KLF5 mRNA, important genes for adipogenesis O’Reilly et al. investigate a long non-coding RNA, named linc-adipose anti-inflammatory (linc-ADAIN), and its role in adipose inflammation and maturation of fat cells (adipocytes). They show that linc-ADAIN’s expression is suppressed in adipose tissue of obese humans and that linc-ADAIN regulates inflammation as well as maturation and size of fat cells.