Transcriptomic changes in response to modulation of long-non-coding RNA LINC00473

Human thermogenic adipose tissue mitigates metabolic disease, raising much interest in understanding its development and function. Here, we show that human thermogenic adipocytes specifically express a primate-specific long non-coding RNA, LINC00473 which is highly correlated with UCP1 expression and decreased in obesity and type-2 diabetes. LINC00473 is detected in progenitor cells, and increases upon differentiation and in response to cAMP. In contrast to other known adipocyte LincRNAs, LINC00473 shuttles out of the nucleus, colocalizes and can be crosslinked to mitochondrial and lipid droplet proteins. Up- or down- regulation of LINC00473 results in reciprocal alterations in lipolysis, respiration and transcription of genes associated with mitochondrial oxidative metabolism. Depletion of PLIN1 results in impaired cAMP-responsive LINC00473 expression and lipolysis, indicating bidirectional interactions between PLIN1, LINC00473 and mitochondrial oxidative functions. Thus, we suggest that LINC00473 is a key regulator of human thermogenic adipocyte function, and reveals a role for a LincRNA in inter-organelle communication and human energy metabolism. To elucidate the mechanisms involved in the generation of thermogenic adipocytes in humans, we searched for major gene expression differences between adipocytes generated from mostly non-thermogenic and thermogenic adipose tissue depots. Biopsies from abdominal subcutaneous (AbdSQ) and from supraclavicular (SClav) adipose tissue of non-diabetic subjects were obtained. Differentiated adipocytes were stimulated for 4h with norepinephrine (NE) prior to RNASeq.