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

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 E , phospholipase A , 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 E 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.

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

“…In addition, the inhibitory effect of TCDD on adipogenesis in C3H10T1/2 cells was shown to be aggravated by the epidermal growth factor (EGF) and the fibroblast growth factor (FGF) that were shown to potentiate AhR activation and the subsequent down-regulation of PPARγ expression [140]. Inhibition of PPARγ by dioxin may be at least partially mediated by the down-regulation of PPARγ coactivator 1 alpha production in murine 3T3-L1 adipocytes [141]. ERK activation was also considered as the potential mechanism of the inhibitory effect of TCDD on PPARγ1 expression in C3H10T1/2 cells [142].…”

Bioactive Fraction of Aronia melanocarpa Fruit Inhibits Adipogenic Differentiation of Cultured 3T3-L1 Cells

“…The cells were then cultured for 2 days in DMEM containing 10 µg/mL insulin and 10% (v/v) FBS. Finally, they were maintained for an additional 2 days in DMEM containing only 10% (v/v) FBS [23].…”

“…Cell viability in ABF ® was measured using the EZ-CYTOX kit (Daeil Lab Service Co., Seoul, South Korea), according to the manufacturer's instructions [23,24]. 3T3-L1 cells were seeded in 24-well plates at a density of 2 × 10 4 cells/well.…”

“…To explore the effects of ABF ® on lipid accumulation in 3T3-L1 adipocytes, lipid accumulation in the cells was measured by Oil Red O staining [23]. Differentiation-induced 3T3-L1 pre-adipocytes were washed with phosphate-buffered saline (PBS, pH 7.4, 135 mM NaCl, 2.7 mM KCl, 4.3 mM NaPO 4 , and 1.4 mM KH 2 PO 4 ) and fixed in 4% formaldehyde (Junsei, Tokyo, Japan) for 1 h at room temperature.…”

Atheroprotective Effects of Glycyrrhiza glabra L.

“…In addition, GA exhibits an endothelial protective effect, protecting the endothelium from advanced glycation end-product-induced damage by inhibiting the receptor for advanced glycation end-products/NF-κB pathway, and is thought to be important in the prevention and treatment of diabetic vascular complications [ 18 ]. Some compounds isolated from licorice exhibited peroxisome proliferator-activated receptor gamma (PPARγ) ligand-binding activity, decreased adipocyte size, and increased PPARγ mRNA expression levels in white adipose tissue [ 19 , 20 ]. Studies have demonstrated the antitumor activity of licorice; in particular, glycyrrhizin induces the apoptosis of cancer cells through caspase- and mitochondria-dependent pathways [ 21 , 22 ].…”