title: 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.
authors: Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih Chien University, Taipei, Taiwan.
authors: Man-Ru
authors: MR
authors: Wu
authors: Ming-Hon
authors: MH
authors: Hou
authors: Ya-Lin
authors: YL
authors: Lin
authors: Chia-Feng
authors: CF
authors: Kuo
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D019440:Anti-Obesity Agents; D001547:Benzaldehydes / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D010944:Plants / Q000737:chemistry
chemical_list: D019440:Anti-Obesity Agents; D001547:Benzaldehydes; D052246:Cyclooxygenase 2 Inhibitors; C034031:2,4,5-trimethoxybenzaldehyde