Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis

Nutrients - Tập 12 Số 5 - Trang 1242
Dae Young Jung1, Ji-Hyun Kim1, Myeong Ho Jung1
1Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea

Tóm tắt

Tanshinone I (Tan I) is a diterpenoid isolated from Salvia miltiorrhiza Bunge and exhibits antitumor effects in several cancers. However, the anti-obesity properties of Tan I remain unexplored. Here, we evaluated the anti-obesity effects of Tan I in high-fat-diet (HFD)-induced obese mice and investigated the underlying molecular mechanisms in 3T3-L1 cells. HFD-induced obese mice were orally administrated Tan I for eight weeks, and body weight, weight gain, hematoxylin and eosin staining and serum biological parameters were examined. The adipogenesis of 3T3-L1 preadipocytes was assessed using Oil Red O staining and measurement of intracellular triglyceride (TG) levels, and mitotic clonal expansion (MCE) and its related signal molecules were analyzed during early adipogenesis of 3T3-L1 cells. The administration of Tan I significantly reduced body weight, weight gain, and white adipocyte size, and improved obesity-induced serum levels of glucose, free fatty acid, total TG, and total cholesterol in vivo in HFD-induced obese mice. Furthermore, Tan I-administered mice demonstrated improvement of glucose metabolism and insulin sensitivity. Treatment with Tan I inhibited the adipogenesis of 3T3-L1 preadipocytes in vitro, with this inhibition mainly occurring at an early phase of adipogenesis through the attenuation of MCE via cell cycle arrest at the G1/S phase transition. Tan I inhibited the phosphorylation of p38, extracellular signal-regulated kinase (ERK), and Akt during the process of MCE, while it stimulated the phosphorylation of AMP-activated protein kinase. Furthermore, Tan I repressed the expression of CCAAT-enhancer-binding protein β (C/EBPβ), histone H3K9 demethylase JMJD2B, and subsequently cell cycle genes. Moreover, Tan I regulated the expression of early adipogenic transcription factors including GATAs and Kruppel-like factor family factors. These results indicate that Tan I prevents HFD-induced obesity via the inhibition of early adipogenesis, and thus improves glucose metabolism and insulin sensitivity. This suggests that Tan I possesses therapeutic potential for the treatment of obesity and obesity-related diseases.

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Tài liệu tham khảo

Jo, J., Gavrilova, O., Pack, S., Jou, W., Mullen, S., and Periwal, V. (2009). Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth. PLoS Comput. Biol.

Rosen, 2006, Adipocyte differentiation from the inside out, Nat. Rev. Mol. Cell Biol., 7, 885, 10.1038/nrm2066

Tang, 2003, Mitotic clonal expansion: A synchronous process required for adipogenesis, Proc. Natl. Acad. Sci. USA, 100, 44, 10.1073/pnas.0137044100

Bost, 2005, The role of MAPKs in adipocyte differentiation and obesity, Biochimie, 87, 51, 10.1016/j.biochi.2004.10.018

Farmer, 2006, Transcriptional control of adipocyte formation, Cell Metab., 4, 263, 10.1016/j.cmet.2006.07.001

Zhou, 2005, Danshen: An overview of its chemistry, pharmacology, pharmacokinetics, and clinical use, J. Clin. Pharmacol., 45, 1345, 10.1177/0091270005282630

Jang, 2017, Gomisin N inhibits adipogenesis and prevents high-fat diet-induced obesity, Sci. Rep., 7, 40345, 10.1038/srep40345

Wang, 2015, Wnt/β-Catenin Mediates AICAR Effect to Increase GATA3 Expression and Inhibit Adipogenesis, J. Biol. Chem., 290, 19458, 10.1074/jbc.M115.641332

Guo, 2015, Transcriptional regulation of adipocyte differentiation: A central role for CCAAT/enhancer-binding protein (C/EBP) β, J. Biol. Chem., 290, 755, 10.1074/jbc.R114.619957

Guo, 2012, Histone demethylase Kdm4b functions as a co-factor of C/EBPβ to promote mitotic clonal expansion during differentiation of 3T3-L1 preadipocytes, Cell Death Differ., 19, 1917, 10.1038/cdd.2012.75

Chang, E., and Kim, C.Y. (2019). Natural Products and Obesity: A Focus on the Regulation of Mitotic Clonal Expansion during Adipogenesis. Molecules, 24.

Prusty, 2002, Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes, J. Biol. Chem., 27, 46226, 10.1074/jbc.M207776200

Tang, 2005, Sequential phosphorylation of CCAAT enhancer-binding protein β by MAPK and glycogen synthase kinase 3β is required for adipogenesis, Proc. Natl. Acad. Sci. USA, 102, 9766, 10.1073/pnas.0503891102

Inoki, 2012, AMPK and mTOR in cellular energy homeostasis and drug targets, Annu. Rev. Pharmacol. Toxico., 52, 381, 10.1146/annurev-pharmtox-010611-134537

Giri, 2006, AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model, Nutr. Metab., 3, 31, 10.1186/1743-7075-3-31

Park, Y.K., Obiang-Obounou, B.W., Lee, J., Lee, T.Y., Bae, M.A., Hwang, K.S., Lee, K.B., Choi, J.S., and Jang, B.C. (2017). Anti-Adipogenic Effects on 3T3-L1 Cells and Zebrafish by Tanshinone IIA. Int. J. Mol. Sci., 18.

Rahman, 2016, Cryptotanshinone, a compound of Salvia miltiorrhiza inhibits pre-adipocytes differentiation by regulation of adipogenesis-related genes expression via STAT3 signaling, Phytomedicine, 23, 58, 10.1016/j.phymed.2015.12.004

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Nutrients

Tập 12 Số 5

1242

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