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LIGHT/TNFSF14 signaling attenuates beige fat biogenesis
Author(s) -
Kou Yanbo,
Liu Qingya,
Liu Wenli,
Sun Hongxiang,
Liang Ming,
Kong Fanyun,
Zhang Bo,
Wei Yanxia,
Liu Zhuanzhuan,
Wang Yugang
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800792r
Subject(s) - adipogenesis , adipose tissue , endocrinology , white adipose tissue , medicine , tumor necrosis factor alpha , cytokine , signal transduction , microbiology and biotechnology , chemistry , biology
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‐β receptor (LTβR) on adipose precursors blocked beige fat biogenesis. LTβR signals attenuated the JNK pathway, which contributed to their antibeiging effect. Blocking JNK activation using a small molecular inhibitor prevented cold‐induced scWAT beiging. Furthermore, LIGHT/LTβR signals acted as an attenuator of white 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 LIGHT signaling functions as a mechanism to divert energy in favor of immune activation.—Kou, Y., Liu, Q., Liu, W., Sun, H., Liang, M., Kong, F., Zhang, B., Wei, Y., Liu, Z., Wang, Y. LIGHT/TNFSF14 signaling attenuates beige fat biogenesis. FASEB J. 33, 1595–1604 (2019). www.fasebj.org