Dibenzoylmethane Suppresses Lipid Accumulation and Reactive Oxygen Species Production through Regulation of Nuclear Factor (Erythroid-Derived 2)-Like 2 and Insulin Signaling in Adipocytes

Abstract

The aim of this study was to investigate the effects of dibenzoylmethane (1,3-diphenyl-1,3-propanedione, DBM) from licorice roots on lipid accumulation and reactive oxygen species (ROS) production in 3T3-L1 cells. DBM effectively inhibited lipid accumulation during adipogenesis, and its inhibitory effect was shown to be due to the down-regulation of adipogenic factors such as CCAAT-enhancer-binding protein-α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and fatty acid-binding protein 4 (FABP4). DBM was observed to exert its inhibitory effect on lipid accumulation in the early adipogenic stage (days 0-2) by regulating early adipogenic factors including CCAAT-enhancer-binding protein-β (C/EBPβ) and Krueppel-like factor (KLF) 2. DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling.

Punicalagin, a Pomegranate‐Derived Ellagitannin, Suppresses Obesity and Obesity‐Induced Inflammatory Responses Via the Nrf2/Keap1 Signaling Pathway

“…3T3‐L1 cells were grown and maintained in DMEM containing 10% BS and 1% PS. Two days after confluency, adipocyte differentiation (adipogenesis) was induced and processed as previously described . RAW264.7 cells, a murine blood macrophage cell line, were plated at 2 × 10 5 cells per well and cultured in 10% FBS/1% PS‐supplemented DMEM.…”

“…RAW264.7 or 3T3‐L1 cells (1.5 × 10 4 cells per well) were incubated in a 96‐well plate for 24 h. Cells were pretreated with PCG (1–10 µ m ) for 2 h, after which the medium was replaced with ACM. After 24–48 h, the MTT assay was performed as previously described …”

“…Reactive oxygen species (ROS) production was measured using dichloro‐dihydro‐fluorescein diacetate (DCFH‐DA) assay as previously described . Hydrogen peroxide (50 µM) and N ‐acetyl cysteine (NAC, 5 mM) were used as negative and positive controls, respectively.…”

“…Protein expression in cells or tissues was examined as previously described . Protein signals were detected by LAS imaging software (Fuji, New York, NY, USA).…”

Dibenzoylmethane, a Component of Licorice, Suppresses Monocyte-to-Macrophage Differentiation and Inflammatory Responses in Human Monocytes and Mouse Macrophages

“…In addition, ROS generation has also been a mechanism associated with the monocyte-tomacrophage differentiation. [42][43][44] Many studies showed that ROS is critically produced during macrophage differentiation, but ROS removal or elimination blocks the macrophage differentiation. [42][43][44] Based on our previous study showing that DBM suppressed intracellular ROS generations, 45) DBM-mediated inhibition of differentiation of monocyte to macrophage is also considered to be due to the ROS regulation.…”