Isoeugenol Inhibits Adipogenesis in 3T3-L1 Preadipocytes with Impaired Mitotic Clonal Expansion

• Published in: Nutrients 2024-04, Vol.16 (9), p.1262
• Main Authors: Choi, Yae Rim, Na, Hyun-Jin, Lee, Jaekwang, Kim, Young-Suk, Kim, Min Jung
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipogenesis - drug effects; Animals; anti-adipogenesis; Antioxidants; Antioxidants - pharmacology; CCAAT-Enhancer-Binding Protein-alpha - genetics; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Cell cycle; cell cycle arrest; Cell Differentiation - drug effects; Cell growth; Cell Proliferation - drug effects; Cyclin-dependent kinases; Dexamethasone; Enzymes; Eugenol - analogs & derivatives; Eugenol - pharmacology; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - metabolism; Insulin; isoeugenol; Kinases; Lipid Metabolism - drug effects; Lipids; Liver diseases; Mice; Mitosis - drug effects; mitotic clonal expansion (MCE); Obesity; PPAR gamma - metabolism; Proteins; Reactive oxygen species; reactive oxygen species (ROS); Reactive Oxygen Species - metabolism; Scientific equipment and supplies industry; Software; Superoxide; Transcription factors; Variance analysis
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16091262

Isoeugenol (IEG), a natural component of clove oil, possesses antioxidant, anti-inflammatory, and antibacterial properties. However, the effects of IEG on adipogenesis have not yet been elucidated. Here, we showed that IEG blocks adipogenesis in 3T3-L1 cells at an early stage. IEG inhibits lipid accumulation in adipocytes in a concentration-dependent manner and reduces the expression of mature adipocyte-related factors including PPARγ, C/EBPα, and FABP4. IEG treatment at different stages of adipogenesis showed that IEG inhibited adipocyte differentiation by suppressing the early stage, as confirmed by lipid accumulation and adipocyte-related biomarkers. The early stage stimulates growth-arrested preadipocytes to enter mitotic clonal expansion (MCE) and initiates their differentiation into adipocytes by regulating cell cycle-related factors. IEG arrested 3T3-L1 preadipocytes in the G /G phase of the cell cycle and attenuated cell cycle-related factors including cyclinD1, CDK6, CDK2, and cyclinB1 during the MCE stage. Furthermore, IEG suppresses reactive oxygen species (ROS) production during MCE and inhibits ROS-related antioxidant enzymes, including superoxide dismutase1 (SOD1) and catalase. The expression of cell proliferation-related biomarkers, including pAKT and pERK1/2, was attenuated by the IEG treatment of 3T3-L1 preadipocytes. These findings suggest that it is a potential therapeutic agent for the treatment of obesity.