RT Journal Article
SR Electronic
T1 A long-non-coding RNA, <em>LINC00473</em>, confers the human adipose tissue thermogenic phenotype through enhanced cAMP responsiveness
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 339192
DO 10.1101/339192
A1 Khanh-Van Tran
A1 Cecilie Nandrup-Bus
A1 Tiffany DeSouza
A1 Ricardo Soares
A1 Naja Zenius Jespersen
A1 So Yun Min
A1 Raziel Rojas-Rodriguez
A1 Hanni Willenbrock
A1 Therese Juhlin
A1 Mai Charlotte Krogh Severinsen
A1 Kimberly Malka
A1 Bente Klarlund Pedersen
A1 Timothy Fitzgibbons
A1 Camilla Scheele
A1 Silvia Corvera
A1 Søren Nielsen
YR 2018
UL http://biorxiv.org/content/early/2018/06/05/339192.abstract
AB Specialized adipocytes localized in distinct depots mediate the many physiological functions of adipose tissue. In humans, paucity of thermogenic adipocytes correlates with high metabolic disease risk, raising much interest in the mechanisms by which these cells arise. Here we report molecular signatures associated with adipocyte development in different human depots and identify a long non-coding RNA, LINC00473, as the transcript most closely associated with enrichment of thermogenic adipocytes. LINC00473 expression is low in subjects with obesity or type-2 diabetes and is highly correlated with cAMP signaling and mitochondrial oxidative phosphorylation pathways. LINC00473 is localized in the nucleus and the cytoplasm, and its knockdown impairs induction of UCP1 and mitochondrial respiration. These results reveal that depot-enriched genes that modulate responsiveness to external stimuli, specifically LINC00473, are important determinants of the adipose tissue thermogenic phenotype, and potential targets for metabolic disease therapy.