The long noncoding RNA ADIPINT is a gatekeeper of pyruvate carboxylase function regulating human fat cell metabolism

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

Nyckelord

long noncoding RNA

pyruvate carboxylase

metabolic homeostasis

Bioteknologi

Biotechnology

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)