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The long noncoding RNA ADIPINT is a gatekeeper of pyruvate carboxylasefunction regulating human fat cell metabolism
karolinska institutet.ORCID iD: 0000-0003-2085-1542
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH). (Carsten Mim)ORCID iD: 0000-0003-1854-0497
karolinska institutet.
karolinska institutet.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The pleiotropic function of long noncoding RNAs (lncRNAs) is well recognized,but their direct role in governingmetabolic homeostasis is less understood. Herein,we describe a human adipocyte-specific lncRNA, ADIPINT, that regulatespyruvate carboxylase (PC) an enzyme pivotal to energy metabolism. With a novelapproach, Targeted RNA-protein identification using Orthogonal Organic PhaseSeparation (TROOPS) and validation with electron microscopy, we show thatADIPINT binds to PC. ADIPINT knockdown alters the interactome anddecreases the mitochondrial abundance and enzymatic activty of PC. Decreases inADIPINT or PC expression reduce adipocyte lipid synthesis, breakdown and lipidcontent. In human white adipose tissue, ADIPINT expression is increased inobesity, linked to fat cell size, adipose insulin resistance and PC activity. Thus, weidentify ADIPINT as a regulator of lipid metabolism in human white adipocytes,which at least in part is mediated through its interaction with PC.

Keywords [en]
long noncoding RNAs, pyruvate carboxylase
National Category
Medical and Health Sciences
Research subject
Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-304510OAI: oai:DiVA.org:kth-304510DiVA, id: diva2:1608996
Note

QC 20211108

Available from: 2021-11-05 Created: 2021-11-05 Last updated: 2022-06-25Bibliographically approved

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Wang, ZuonengMim, Carsten

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