Metabolic regulation of transcription through compartmentalized NAD + biosynthesis

Abstract

Integrating glucose and fat Consuming too much glucose makes you fat, but it is unclear how this conversion is mediated by the body. Glycolysis links to gene transcription via the essential coenzyme nicotinamide adenine dinucleotide in its oxidized state (NAD + ). Ryu et al. found that compartmentalized NAD + synthesis and consumption integrate glucose metabolism and adipogenic (fat-promoting) transcription during adipocyte differentiation (see the Perspective by Trefely and Wellen). Competition between the NAD + precursors—nuclear NMNAT-1 and cytosolic NMNAT-2—for their common substrate, nicotinamide mononucleotide, regulates the balance between nuclear NAD + synthesis for adipogenic gene regulation and cytosolic NAD + synthesis used in metabolism. Science , this issue p. eaan5780 ; see also p. 603