Original Article
International Journal of Obesity advance online publication 27 October 2009; doi: 10.1038/ijo.2009.223
Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes
E J Bak1,2,5, H G Park1,2,3,5, J M Kim1,2,4, J M Kim3, Y-J Yoo1,2,4 and J-H Cha1,2,4
- 1BK21 Project, Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, Korea
- 2Research Center for Orofacial Hard Tissue Regeneration, College of Dentistry, Yonsei University, Seoul, Korea
- 3Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea
- 4Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, Korea
Correspondence: Professor J-H Cha, Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, 134 Sinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea. E-mail: Jcha@yuhs.ac
5These authors contributed equally to this work.
Received 2 June 2009; Revised 31 August 2009; Accepted 7 September 2009; Published online 27 October 2009.
Abstract
Objective:
Evodiamine (evo) has been shown to exert anti-inflammatory, antinociceptive and anticancer effects. In this study, we investigated the effects of evo alone and in combination with rosiglitazone (rosi) on in vitro adipocyte differentiation and in vivo obesity related to diabetes.
Methods:
Adipocyte differentiation was investigated in vitro using 3T3-L1 and C3H10T1/2 cells. To determine the degree of differentiation, Oil Red O staining and reverse transcription–PCR were carried out. Four groups of db/db mice were treated intraperitoneally once per day with vehicle, evo, rosi and evo+rosi. The mice were killed after 14 days and the blood, liver and adipose tissue were analyzed.
Results:
The presence of evo or evo combined with rosi during adipogenic induction has been shown to inhibit adipocyte differentiation to a significant degree, particularly at the commitment and early induction stages. The evo and evo+rosi groups of db/db mice evidenced significant reductions in body weight gain. The ratio of epididymal white adipocyte tissue weight to body weight of the evo group was also significantly reduced. It is important to note that in the evo+rosi treatment, blood glucose levels were reduced to a degree similar to that of the rosi group, and plasma insulin levels were reduced significantly better than that of rosi group. Furthermore, hepatic lesions associated with fat and glycogen deposition were morphologically improved in the evo and evo+rosi groups.
Conclusion:
The results of this study showed that evo exerts an inhibitory effect on in vitro adipocyte differentiation and in vivo obesity, and also an improvement effect on insulin resistance. These desirable effects of evo were noted even in the presence of rosi. These results indicate that evo improves the undesirable effects of rosi, including adipogenesis, body weight gain and hepatotoxicity, while preserving its desirable blood-glucose-lowering effect.
Keywords:
evodaimine, adipocyte differentiation, rosiglitazone, diabetes
