LIGHT/TNFSF14 signaling attenuates beige fat biogenesis

Abstract

The physiologic signals that regulate beige adipogenesis remain incompletely understood, especially those that limit browning and prevent overexpenditure of energy. In this study, the TNF family member cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT), also known as TNF super family protein 14 (TNFSF14), can inhibit adipose precursor differentiation into beige adipocytes. In acute cold stress, LIGHT deficiency in mice accelerated browning in the subcutaneous white adipose tissue (scWAT). Further experiments showed that LIGHT interacting with lymphotoxin-b receptor (LTbR) on adipose precursors blocked beige fat biogenesis. LTbR signals attenuated the JNK pathway, which contributed to their antibeiging effect. Blocking JNK activation using a smallmolecular inhibitor prevented cold-induced scWAT beiging. Furthermore, LIGHT/LTbRsignals acted as anattenuator ofwhite adipogenesis. LIGHT deficiency in mice promoted obesity during high-fat diet feeding. These findings identify the LIGHT axis as a regulator of adipose tissue homeostasis and suggest that LIGHTsignaling functions as amechanismtodivert energy in favor of immune activation.