Anti-obesity effects of KR-66195, a synthetic DPP-IV inhibitor, in diet-induced obese mice and obese-diabetic ob/ob mice

Eun Young Lee, Yeon Wook Kim, Hyunhee Oh, Cheol Soo Choi, Jin Hee Ahn, Byung Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee

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4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)793-799
Number of pages7
JournalMetabolism: Clinical and Experimental
Volume63
Issue number6
DOIs
Publication statusPublished - 2014 Jun

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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