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

Yan-Bo Kou1, Xiao-Qing Yan2, Qi-Yue Jing1

  • 1Jiangsu Key Laboratory of Immunity and Metabolism, Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China.

Biochemical and Biophysical Research Communications
|November 4, 2021
PubMed

Insights

Lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT) deficiency improves glucose tolerance. LIGHT regulates glucose uptake in adipose tissue via the LIGHT-LTβR-AKT-GLUT4 axis, impacting glucose homeostasis.

Area of Science:

  • Immunology
  • Metabolic disease
  • Adipocyte biology

Background:

  • Immune-adipose crosstalk influences adipocyte glucose homeostasis.
  • Lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT) is implicated in immune signaling.
  • The role of LIGHT in adipose tissue glucose metabolism requires elucidation.

Purpose of the Study:

  • To investigate the impact of LIGHT on glucose metabolism in adipocytes.
  • To determine the molecular mechanisms by which LIGHT affects glucose uptake.
  • To explore the potential of targeting the LIGHT pathway for metabolic regulation.

Main Methods:

  • Utilized mouse models with LIGHT deficiency and overexpression.
  • Assessed glucose tolerance and glucose consumption in adipose tissue.
  • Investigated the involvement of the AKT pathway and glucose transporter-4 (GLUT4) expression.
  • Examined the interaction between LIGHT and lymphotoxin-β receptor (LTβR).

Main Results:

  • LIGHT deficiency enhanced glucose tolerance and adipose tissue glucose consumption, particularly under high-fat diet conditions.
  • Overexpression of LIGHT inhibited glucose uptake during white adipogenesis.
  • LIGHT, through interaction with LTβR, attenuated the AKT pathway.
  • This attenuation led to reduced glucose transporter-4 (GLUT4) expression and inhibited glucose uptake.

Conclusions:

  • The LIGHT-LTβR-AKT-GLUT4 axis is identified as a key regulator of glucose uptake in adipose tissue.
  • LIGHT plays a significant role in maintaining glucose homeostasis.
  • Targeting LIGHT may offer therapeutic strategies for metabolic disorders.
Keywords:
AdipocyteCytokineGLUT4Glucose uptakeLIGHT

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