Theobromine inhibits differentiation of 3T3-L1 cells during the early stage of adipogenesis via AMPK and MAPK signaling pathways

Obesity is characterized by hypertrophy and/or by the differentiation or adipogenesis of pre-existing adipocytes. In this study, we investigated the inhibitory effects of theobromine, a type of alkaloid in cocoa, on adipocyte differentiation of 3T3-L1 preadipocytes and its mechanisms of action. Theo...

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Bibliographic Details
Published in:Food & function 2015-07, Vol.6 (7), p.2365-2374
Main Authors: Jang, Yeon Jeong, Koo, Hyun Jung, Sohn, Eun-Hwa, Kang, Se Chan, Rhee, Dong-Kwon, Pyo, Suhkneung
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adipocytes - drug effects
Adipocytes - metabolism
Adipogenesis - drug effects
AMP-Activated Protein Kinases - genetics
AMP-Activated Protein Kinases - metabolism
Animals
CCAAT-Enhancer-Binding Protein-alpha - genetics
CCAAT-Enhancer-Binding Protein-alpha - metabolism
Coca - chemistry
Down-Regulation
Interleukin-6 - genetics
Interleukin-6 - metabolism
MAP Kinase Kinase 4 - genetics
MAP Kinase Kinase 4 - metabolism
Mice
Mitogen-Activated Protein Kinase Kinases - genetics
Mitogen-Activated Protein Kinase Kinases - metabolism
Phosphorylation
Plant Extracts - pharmacology
PPAR gamma - genetics
PPAR gamma - metabolism
Theobromine - pharmacology
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Summary:Obesity is characterized by hypertrophy and/or by the differentiation or adipogenesis of pre-existing adipocytes. In this study, we investigated the inhibitory effects of theobromine, a type of alkaloid in cocoa, on adipocyte differentiation of 3T3-L1 preadipocytes and its mechanisms of action. Theobromine inhibited the accumulation of lipid droplets, the expression of PPARγ and C/EBPα, and the mRNA expression of aP2 and leptin. The inhibition of adipogenic differentiation by theobromine occurred primarily in the early stages of differentiation. In addition, theobromine arrested the cell cycle at the G 0 /G 1 phase and regulated the expressions of CDK2, p27, and p21. Theobromine treatment increased AMPK phosphorylation and knockdown of AMPKα1/α2 prevented the ability of theobromine to inhibit PPARγ expression in the differentiating 3T3-L1 cells. Theobromine reduced the phosphorylation of ERK and JNK. Moreover, the secretion and the mRNA level of TNF-α and IL-6 were inhibited by theobromine treatment. These data suggest that theobromine inhibits adipocyte differentiation during the early stages of adipogenesis by regulating the expression of PPARγ and C/EBPα through the AMPK and ERK/JNK signaling pathways in 3T3-L1 preadipocytes. Theobromine decreased the accumulation of lipid droplets in a concentration-dependent manner.
ISSN:2042-6496
2042-650X
DOI:10.1039/c5fo00397k