2,4,5-TMBA, a Natural Inhibitor of Cyclooxygenase-2, Suppresses Adipogenesis and Promotes Lipolysis in 3T3-L1 Adipocytes

Abstract

Obesity is a global health problem. Because of the high costs and side effects of obesity-treatment drugs, the potential of natural products as alternatives for treating obesity is under exploration. 2,4,5-Trimethoxybenzaldehyde (2,4,5-TMBA) present in plant roots, seeds, and leaves was reported to be a significant inhibitor of cyclooxygenase-2 (COX-2) activity at the concentration of 100 μg/mL. Because COX-2 is associated with differentiation of preadipocytes, the murine 3T3-L1 cells were cultured with 100 μg/mL of 2,4,5-TMBA during differentiation and after the cells were fully differentiated to study the effect of 2,4,5-TMBA on adipogenesis and lipolysis. Oil Red O staining and triglyceride assay revealed that 2,4,5-TMBA inhibited the formation of lipid droplets during differentiation; moreover, 2,4,5-TMBA down-regulated the protein levels of adipogenic signaling molecules and transcription factors MAP kinase kinase (MEK), extracellular signal-regulated kinase (ERK), CCAAT/enhancer binding protein (C/EBP)α, β, and δ, peroxisome proliferator-activated receptor (PPAR)γ, adipocyte determination and differentiation-dependent factor 1 (ADD1), and the rate-limiting enzyme for lipid synthesis acetyl-CoA carboxylase (ACC). In fully differentiated adipocytes, treatment with 2,4,5-TMBA for 72 h significantly decreased lipid accumulation by increasing the hydrolysis of triglyceride through suppression of perilipin A (lipid droplet coating protein) and up-regulation of hormone-sensitive lipase (HSL). The results of this in vitro study will pioneer future in vivo studies on antiobesity effects of 2,4,5-TMBA and selective COX-2 inhibitors.

Pharmacological Effects of the Water Fraction of Key Components in the Traditional Chinese Prescription Mai Tong Fang on 3T3-L1 Adipocytes and ob/ob Diabetic Mice

“…The hallmark of adipocyte differentiation is the formation and enlargement of intracellular lipid droplets [20]. In this study, the extract of three herbs milkvetch root, salviae miltiorrhizae and mulberry as key components of MTF effectively decreased the accumulation of lipids in 3T3-L1 cells.…”

N6-(2-Hydroxyethyl)adenosine in the Medicinal Mushroom Cordyceps cicadae Attenuates Lipopolysaccharide-Stimulated Pro-inflammatory Responses by Suppressing TLR4-Mediated NF-κB Signaling Pathways

“…Twenty-four hours after seeding, the cells were treated with LPS (1 μg/mL) and various concentrations of test samples for another 24 h. At the end of the treatment, medium was removed and the cells were cultured with new DMEM containing MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) at a final concentration of 0.5 mg/mL for 4 h. The purple formazan was dissolved by DMSO, and the absorbance at 570 nm was taken. The absorbance is proportional to the viability of cells …”

“…The absorbance is proportional to the viability of cells. 47 Measurement of Pro-inflammatory Mediators. After the cells were treated with various concentrations of test samples for 1 h and LPS for 6 h, the culture medium was collected for the measurement of IL-1β and TNF-α by using ELISA kits purchased from Biolegend (San Diego, CA, USA).…”

2,4,5-Trimethoxybenzaldehyde, a Bitter Principle in Plants, Suppresses Adipogenesis through the Regulation of ERK1

“…Previously, we showed that 2,4,5-TMBA suppresses the differentiation of preadipocytes . In this study, preadipocytes were co-cultured with 2,4,5-TMBA specifically at post-induction days 0–2, 2–4, 4–6, or 6–8 only to further figure out the stages that are critically affected by 2,4,5-TMBA during adipogenesis.…”

“…COX-2 not only plays a role in the inflammatory process but is also involved in the modulation of adipogenesis. , In our previous study, 3T3-L1 preadipocytes and adipocytes were treated with 0.5 mM 2,4,5-TMBA to explore its effect on adipogenesis and lipolysis. The results showed that 2,4,5-TMBA suppressed differentiation of preadipocyts into adipocytes and enhanced lipolysis in mature adipocytes …”