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

Lee EY, Kim YW, Oh H, Choi CS, Ahn JH, Lee BW, Kang ES, Cha BS, Lee HC
Metabolism. 2014 63 (6): 793-9

PMID: 24684824 · DOI:10.1016/j.metabol.2014.02.011

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

MeSH Terms (23)

Animals Anti-Obesity Agents Blood Glucose Body Composition Diabetes Mellitus Diet, High-Fat Dipeptidyl Peptidase 4 Eating Energy Metabolism Enzyme Inhibitors Female Glucagon-Like Peptide 1 Glucose Tolerance Test Male Mice Mice, Inbred C57BL Mice, Obese Obesity Random Allocation Thiazolidines Treatment Outcome Valine Weight Gain

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