Sulforaphane Inhibits Mitotic Clonal Expansion During Adipogenesis Through Cell Cycle Arrest

• Published in: Obesity (Silver Spring, Md.) Vol. 20; no. 7; pp. 1365 - 1371
• Main Authors: Choi, Kyeong‐Mi, Lee, Youn‐Sun, Sin, Dong‐Mi, Lee, Seunghyun, Lee, Mi Kyeong, Lee, Yong‐Moon, Hong, Jin‐Tae, Yun, Yeo‐Pyo, Yoo, Hwan‐Soo
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2012
• Subjects: 3T3-L1 Cells - drug effects; Adipocytes - drug effects; Adipocytes - physiology; Adipogenesis - drug effects; Animals; Anticarcinogenic Agents - pharmacology; Blotting, Western; Body fat; Cell Cycle Checkpoints - drug effects; Cell Differentiation - drug effects; Cell Line; Cell Proliferation - drug effects; Cellular biology; Humans; Isothiocyanates; Mice; Mitosis - drug effects; Obesity; Phytochemicals; PPAR gamma - drug effects; PPAR gamma - metabolism; Proliferating Cell Nuclear Antigen - drug effects; Rats; Thiocyanates - pharmacology; Transcription Factors; Up-Regulation
• ISSN: 1930-7381; 1930-739X; 1930-739X
• DOI: 10.1038/oby.2011.388

Obesity is a risk factor for numerous metabolic disorders such as type 2 diabetes, hypertension, and coronary heart disease. Adipocyte differentiation is triggered by adipocyte hyperplasia, which leads to obesity. In this study, the inhibitory effect of sulforaphane, an isothiocyanate, on adipogenesis in 3T3–L1 cells was investigated. Sulforaphane decreased the accumulation of lipid droplets stained with Oil Red O and inhibited the elevation of triglycerides in the adipocytes (half‐maximal inhibitory concentration = 7.3 µmol/l). The expression of peroxisome proliferator‐activated receptor γ (PPARγ) and CCAAT/enhancer‐binding protein α (C/EBPα), major transcription factors for adipocyte differentiation, was significantly reduced by sulforaphane. The major effects of sulforaphane on the inhibition of adipocyte differentiation occurred during the early stage of adipogenesis. Thus, the expression of C/EBPβ, an early‐stage biomarker of adipogenesis, decreased in a concentration‐dependent manner when the adipocytes were exposed to sulforaphane (0, 5, 10, and 20 µmol/l). The proliferation of adipocytes treated with 20 µmol/l sulforaphane for 24 and 48 h was also suppressed. These results indicate that sulforaphane may specifically affect mitotic clonal expansion to inhibit adipocyte differentiation. Sulforaphane arrested the cell cycle at the G0/G1 phase, increased p27 expression, and decreased retinoblastoma (Rb) phosphorylation. Additionally, sulforaphane modestly decreased the phosphorylation of ERK1/2 and Akt. Our results indicate that the inhibition of early‐stage adipocyte differentiation by sulforaphane may be associated with cell cycle arrest at the G0/G1 phase through upregulation of p27 expression.