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Human thermogenic adipocyte regulation by the long noncoding RNA LINC00473

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Human thermogenic adipose tissue mitigates metabolic disease, thus raising much interest in understanding its development and function. Here, we show that human thermogenic adipocytes specifically express a primate-specific long noncoding RNA (lncRNA), LINC00473, which is highly correlated with UCP1 expression and is decreased in obesity and type-2 diabetes. LINC00473 is detected in progenitor cells, and increases following differentiation and in response to cyclic AMP (cAMP). In contrast to other known adipocyte long intergenic noncoding RNAs, LINC00473 shuttles out of the nucleus, colocalizes and can be cross-linked to mitochondrial and lipid droplet proteins. Up- or downregulation 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 among PLIN1, LINC00473 and mitochondrial oxidative functions. Thus, we suggest that LINC00473 is a key regulator of human thermogenic adipocyte function and reveal a role for a lncRNA in interorganelle communication and human energy metabolism.

Original languageEnglish
JournalJournal of Nutrition and Metabolism
Volume2
Issue number5
Pages (from-to)397-412
Number of pages16
ISSN1743-7075
DOIs
Publication statusPublished - May 2020

    Research areas

  • Adipocytes/physiology, Adult, Aged, Aged, 80 and over, Cell Communication/genetics, Cell Nucleus/metabolism, Cells, Cultured, Diabetes Mellitus, Type 2/genetics, Energy Metabolism/genetics, Fatty Acids, Nonesterified/metabolism, Female, Gene Expression Regulation, Humans, Lipid Droplets, Male, Middle Aged, Obesity/genetics, Oxygen Consumption/genetics, Perilipin-1/deficiency, RNA, Long Noncoding/genetics, Thermogenesis/genetics, Uncoupling Protein 1/biosynthesis, Young Adult

ID: 61783442