The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase

The pleiotropic function of long noncoding RNAs is well recognized, but their direct role in governing metabolic homeostasis is less understood. Here, we describe a human adipocyte-specific lncRNA, ADIPINT, that regulates pyruvate carboxylase , a pivotal enzyme in energy metabolism. With a novel approach, Targeted RNA-protein identification using Orthogonal Organic Phase Separation, and validation with electron microscopy, we show that ADIPINT binds to PC. ADIPINT knockdown alters the interactome and decreases the abundance and enzymatic activty of PC in the mitochondria. Reduced ADIPINT or PC expression lowers adipocyte lipid synthesis, breakdown, and lipid content. In human white adipose tissue, ADIPINT expression is increased in obesity and 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.