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Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732

 Yoo Mee Kim  ;  Juan Ji An  ;  Sung-Kil Lim  ;  Hyun Chul Lee  ;  Bong Soo Cha  ;  Yumie Rhee  ;  Yong-Jun Jin 
 Journal of Molecular Endocrinology, Vol.38(4) : 455-465, 2007 
Journal Title
 Journal of Molecular Endocrinology 
Issue Date
The systemic treatment with angiogenesis inhibitor has been shown to result in weight reduction and adipose tissue loss in various models of obesity. To verify the mechanism of CKD-732 (TNP-470 analog) against obesity, we evaluated CKD-732’s peripheral and central anti-obesity effects. CKD-732 was injected subcutaneously (s.c.) for 7 days in various animal models and intracerebroventricularly (i.c.v.) in arcuate nucleus (ARC) lesion mice, ob/ob mice, and normal littermates. Modulation of the hypothalamic neuropeptide mRNAs after i.c.v. injection was evaluated in ARC lesion mice and normal littermates. A conditioned taste aversion (CTA) was performed using lithium chloride (LiCl) as a positive control agent in Long–Evans Tokushima Otsuka and Otsuka Long–Evans Tokushima fatty (OLETF) rats. As a result, 7 days of CKD-732 s.c. injection reduced the cumulative food intake and the body weight significantly in both treated obese (e.g. 114.8 ± 13.4 g vs 170.7 ± 20.6 g, 7.9 ± 0.5% decrease vs 0.3 ± 2.2% decrease; in treated OLETF rat versus control OLETF rat, P < 0.01 respectively) and non-obese models. Epididymal and mesenteric fat pads, and the size of adipocytes were significantly decreased in treated rats. A single i.c.v. injection decreased food intake and body weight in ARC lesion mice and ob/ob mice but not in normal littermates. Unexpectedly, the hypothalamic neuropeptide mRNAs were not altered by single i.c.v. injection. CKD-732 also induced a dose-dependent CTA comparable with LiCl injection, which is a commonly used agent to produce a CTA. In conclusion, CKD-732 causes significant body weight and appetite reduction, possibly by decreasing adiposity directly and inducing central anorexia, which is partly explained by a CTA. These results should be carefully verified to assess the utility of CKD-732 as an anti-obesity drug.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yoo Mee(김유미)
Rhee, Yumie(이유미) ORCID logo https://orcid.org/0000-0003-4227-5638
Lee, Hyun Chul(이현철)
Lim, Sung Kil(임승길)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
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