Anti-obesity effects of KR-66195, a synthetic DPP-IV inhibitor, in diet-induced obese mice and obese-diabetic ob/ob mice
- Authors
- Lee, Eun Young; Kim, Yeon Wook; Oh, Hyunhee; Choi, Cheol Soo; Ahn, Jin Hee; Lee, Byung-Wan; Kang, Eun Seok; Cha, Bong Soo; Lee, Hyun Chul
- Issue Date
- Jun-2014
- Publisher
- W B SAUNDERS CO-ELSEVIER INC
- Keywords
- Diabetes; Obesity; Glucagon-like peptide (GLP)-1; KR-66195; Dipeptidyl peptidase (DPP)-IV
- Citation
- METABOLISM-CLINICAL AND EXPERIMENTAL, v.63, no.6, pp.793 - 799
- Journal Title
- METABOLISM-CLINICAL AND EXPERIMENTAL
- Volume
- 63
- Number
- 6
- Start Page
- 793
- End Page
- 799
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12589
- DOI
- 10.1016/j.metabol.2014.02.011
- ISSN
- 0026-0495
- Abstract
- Objective. We investigated whether KR-66195, a new synthetic dipeptidyl dipeptidase IV inhibitor, could prevent weight gain, as well as improving glycemic control in diet-induced obese (DIO) and ob/ob mice. Materials/Methods. Male C57BL/6 mice were randomly assigned to the following groups: chow diet, high-fat diet, and high-fat diet with KR-66195. After KR-66195 treatment for eight weeks, intraperitoneal glucose tolerance tests were performed. A pair-feeding study was performed to investigate the mechanisms of the anti-obesity effects of KR-66195 in DIO mice. Female ob/ob mice were treated with KR-66195 for three weeks and compared to the vehicle-treated group. Results. In DIO mice, KR-66195 treatment increased the plasma glucagon-like peptide (GLP)-1 levels and improved glucose tolerance. This treatment also reduced body weight gain (5.38 +/- 0.94 g vs. 12.08 +/- 0.55 g, P < 0.01) and food intake (2.41 +/- 0.09 g vs. 2.79 +/- 0.11 g, P < 0.05). In ob/ob mice, KR-66195 treatment for three weeks resulted in comparable effects in DIO mice. In the pair-feeding study, KR-66195-treated mice exhibited a 16% increase in energy expenditure (kcal/h/kg lean body mass) without significant differences in body weight or activities compared with pair-fed mice. These results suggest that KR-66195 prevented weight gain in DIO mice by decreasing food intake, as well as increasing energy expenditure. Conclusions. KR-66195 markedly increased plasma levels of GLP-1, resulting in the probable improvement in glucose tolerance and reduced body weight and food intake. Thus, KR-66195 might be further developed as a therapeutic drug to treat obesity, as well as diabetes. (C) 2014 Elsevier Inc. All rights reserved.
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