LIGHT (TNFSF14) inhibits glucose uptake of adipocytes by downregulating GLUT4 expression via AKT signaling pathway

Yan-Bo Kou; Xiao-Qing Yan; Qi-Yue Jing; Sheng-Han Zhang; Zhuan-Zhuan Liu; Yan-Xia Wei; Yu-Gang Wang

doi:10.1016/j.bbrc.2021.10.061

LIGHT (TNFSF14) inhibits glucose uptake of adipocytes by downregulating GLUT4 expression via AKT signaling pathway

Biochem Biophys Res Commun. 2021 Oct 28:583:106-113. doi: 10.1016/j.bbrc.2021.10.061. Online ahead of print.

Authors

Yan-Bo Kou¹, Xiao-Qing Yan², Qi-Yue Jing³, Sheng-Han Zhang³, Zhuan-Zhuan Liu³, Yan-Xia Wei³, Yu-Gang Wang⁴

Affiliations

¹ Jiangsu Key Laboratory of Immunity and Metabolism, Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China. Electronic address: kyb2015@xzhmu.edu.cn.
² Laboratory of Emergency Medicine, Second Clinical Medical College, Xuzhou Medical University, Xuzhou, China.
³ Jiangsu Key Laboratory of Immunity and Metabolism, Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China.
⁴ Jiangsu Key Laboratory of Immunity and Metabolism, Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China. Electronic address: wangyg@xzhmu.edu.cn.

PMID: 34735871
DOI: 10.1016/j.bbrc.2021.10.061

Abstract

Glucose homeostasis of adipocytes could be regulated by immune-adipose crosstalk. In order to investigate the effects of Lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT) on glucose metabolism, we performed the present study. Our results showed that LIGHT deficiency improved glucose tolerance and enhanced glucose consumption of inguinal white adipose tissue (iWAT) under high fat diet. Consistently, Light overexpression could inhibit glucose uptake during the process of white adipogenesis. Mechanistically, LIGHT interacted with lymphotoxin-β receptor (LTβR) to attenuate AKT pathway leading to downregulation of glucose transporter-4 (GLUT4) expression, which resulted in glucose uptake inhibition. In summary, our findings revealed LIGHT-LTβR-AKT-GLUT4 axis as a regulator of glucose uptake in adipose tissue, which suggested the pivotal role of LIGHT in maintaining glucose homeostasis.

Keywords: Adipocyte; Cytokine; GLUT4; Glucose uptake; LIGHT.