The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking
Open Access
- 14 July 2021
- journal article
- research article
- Published by MDPI AG in Biomolecules
- Vol. 11 (7), 1025
- https://doi.org/10.3390/biom11071025
Abstract
Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.Keywords
Funding Information
- Ministry of Science and Technology, Taiwan (MOST-107-2320-B-182-016-MY3)
- Chang Gung Memorial Hospital (CMRPD1K0051-2)
This publication has 49 references indexed in Scilit:
- Efficient stabilization of natural curcuminoids mediated by oil body encapsulationRSC Advances, 2013
- Curcumin and obesityBioFactors, 2013
- Effects of Supplementation with Curcuminoids on Dyslipidemia in Obese Patients: A Randomized Crossover TrialPhytotherapy Research, 2012
- Anti-Obesity Drugs: A Review about Their Effects and SafetyDiabetes & Metabolism Journal, 2012
- Curcumin inhibits adipocyte differentiation through modulation of mitotic clonal expansionThe Journal of Nutritional Biochemistry, 2011
- Live-cell imaging demonstrates rapid cargo exchange between lipid droplets in adipocytesFEBS Letters, 2011
- Structural requirements of flavonoids for the adipogenesis of 3T3-L1 cellsBioorganic & Medicinal Chemistry, 2011
- The anti-obesity effect ofLethariella cladonioidesin 3T3-L1 cells and obese miceNutrition Research and Practice, 2011
- Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjectsNutrition Journal, 2010
- Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanismCarcinogenesis: Integrative Cancer Research, 2007