LncRNA Nron deficiency protects mice from diet-induced adiposity and hepatic steatosis

Obesity, as a worldwide healthcare problem, has attracted more and more attention. Here we identify a long non-coding RNA NRON, which is highly conserved across species, as an important regulator of glucose/lipid meta-bolism and whole-body energy expenditure. Depletion of Nron leads to metabolic benefits in DIO (diet-induced obesity) mice, including reduced body weight and fat mass, improved insulin sensitivity and serum lipid pa-rameters, attenuated hepatic steatosis and enhanced adipose function. Mechanistically, Nron deletion improves hepatic lipid homeostasis via PER2/Rev-Erb alpha/FGF21 axis coupled with AMPK activation, and enhances adipose function via activating the process of triacylglycerol hydrolysis and fatty acid re-esterification (TAG/FA cycling) and coupled metabolic network. These interactive and integrative effects cooperatively account for a healthier metabolic phenotype in NKO (Nron knockout) mice. Genetic or pharmacological inhibition of Nron may have potential for future therapy of obesity.

Automated summary

This study identifies a long non-coding RNA NRON as an important regulator of glucose/lipid metabolism and whole-body energy expenditure. Depletion of Nron in obese mice leads to metabolic benefits, including reduced body weight and fat mass, improved insulin sensitivity and serum lipid parameters, attenuated hepatic steatosis, and enhanced adipose function. The mechanism involves the activation of specific signaling pathways and metabolic networks. Inhibition of Nron may have potential as a therapeutic approach for obesity.