Glabridin attenuates antiadipogenic activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in murine 3T3-L1 adipocytes

J Appl Toxicol. 2018 Nov;38(11):1426-1436. doi: 10.1002/jat.3664. Epub 2018 Jul 26.

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has various toxicological effects in adipose tissue. Evidence is accumulating that glabridin, a flavonoid extracted from licorice, has beneficial effects on the regulation of glucose homeostasis. In this study, we investigated whether glabridin suppresses TCDD-induced loss of adipogenic action using 3T3-L1 adipocytes as a cell culture model of wasting syndrome. Glabridin effectively suppressed TCDD-induced loss of lipid accumulation in this model. Pretreating cells with glabridin increased the gene expression of not only the adipogenesis-associated key transcription factors peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha, but also lipoprotein lipase in the presence of TCDD. TCDD decreased insulin-stimulated glucose uptake, which was effectively restored by pretreatment with glabridin. Glabridin also inhibited the TCDD-driven decreased production of insulin receptor substrate 1 and glucose transporter 4. TCDD increased the production of mitochondrial superoxides, prostaglandin E2 , phospholipase A2 , cyclooxygenase-1 and intracellular calcium concentrations, while reducing the production of PPARγ coactivator 1 alpha and glycolysis. However, glabridin treatment reduced these TCDD-induced effects. We conclude that glabridin suppresses the TCDD-induced loss of lipid accumulation in 3T3-L1 adipocytes by regulating the levels of PPARγ, CCAAT/enhancer binding protein alpha, lipoprotein lipase, glucose uptake, prostaglandin E2 and energy metabolism. These results also provide in vitro evidence of the effects of glabridin on adipocyte metabolism, which suggests a protective effect against dioxin exposure in the development of insulin resistance and diabetes.

Keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin; 3T3-L1 adipocyte; differentiation; glabridin; prostaglandin E2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Adipogenesis / genetics
  • Animals
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / toxicity*
  • Gene Expression / drug effects
  • Isoflavones / pharmacology*
  • Lipid Metabolism / drug effects
  • Mice
  • Phenols / pharmacology*
  • Polychlorinated Dibenzodioxins / toxicity*

Substances

  • Environmental Pollutants
  • Isoflavones
  • Phenols
  • Polychlorinated Dibenzodioxins
  • glabridin