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

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

Author information

1
Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
2
Department of Biomedical Laboratory Science, College of Health Sciences, Cheongju University, Cheongju, Chungbuk, 28503, Republic of Korea.
3
Department of Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
4
Department of Endocrinology & Metabolism, Kyung Hee University Hospital, Seoul, 02447, Republic of Korea.
5
Department of Physiology, Kyung Hee University, College of Medicine, Seoul, 02447, Republic of Korea.

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

PMID:
30051472
DOI:
10.1002/jat.3664

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