Pioglitazone-induced body weight gain is prevented by combined administration with the lipoprotein lipase activator NO-1886 |
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| Authors: | Kusunoki Masataka Tsutsumi Kazuhiko Sato Daisuke Nakamura Aki Habu Satoshi Mori Yuichi Morishita Munehiko Yonemoto Takayuki Miyata Tetsuro Nakaya Yutaka Nakamura Takao |
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| Institution: | aDepartment of Internal Medicine, Medical Clinic, Aichi Medical University, 2-12-1, Higashisakura, Higashi-ku, Nagoya 461-0005, Japan;bOkinaka Memorial Institute for Medical Research, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470, Japan;cDepartment of Biomedical Information Engineering, Graduate School of Medical Science, Yamagata University, 2-2-2, Iida-nishi, Yamagata 990-9585, Japan;dDepartment of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School, 3-8-15, Kuramoto-cho, Tokushima 770-8503, Japan;eDivision of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, Faculty of Medicine, Aichi Medical University, 21, Karimata, Yazako, Nagakute-cho, Aichi 480-1195, Japan;fDepartment of Nutrition, Faculty of Wellness, Shigakkan University, 55, Nadakayama, Yokonemachi, Ohbu, Aichi 474-8651, Japan;gDepartment of Vascular Surgery, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan |
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| Abstract: | Pioglitazone improves insulin resistance in diabetics but often causes body weight gain. The lipoprotein lipase activator NO-1886 has been shown to exert both anti-obesity and anti-insulin-resistance effects. In this study, we investigated the effect of the combined administration of pioglitazone with NO-1886 (pioglitazone + NO-1886) in preventing body weight gain in insulin-resistant, high-fat fed rats. The rats were fed a standard or high-fat diet for 16 weeks. The high-fat fed rats were randomized at week 9 into 4 groups (i.e., control, pioglitazone (30 mg/kg/day), NO-1886 (100 mg/kg/day), and pioglitazone + NO-1886 (30 and 100 mg/kg/day, respectively)). The high-fat fed control rats developed obesity and insulin resistance. After 7 weeks of drug treatment, pioglitazone + NO-1886 was found to prevent the body weight gain caused by pioglitazone alone (pioglitazone + NO-1886: Δ76.0 ± 16.8 g vs. pioglitazone: Δ127.8 ± 39.5 g, P < 0.05) and to increase glucose infusion rate during insulin clamp, compared with the results in the high-fat fed control group. No differences in plasma nonesterified fatty acid, leptin, adiponectin, glucose, or insulin levels were observed between the pioglitazone + NO-1886 and the pioglitazone-alone groups. However, plasma total cholesterol and HDL-cholesterol levels were significantly increased and plasma triglyceride levels were slightly decreased in the pioglitazone + NO-1886 group, compared with the values in the pioglitazone-alone group. In summary, the combined administration of pioglitazone and NO-1886 prevented the pioglitazone-induced body weight gains and ameliorated insulin resistance observed in high-fat fed rats. These results indicate that combined therapy with pioglitazone and NO-1886 may be beneficial for the treatment of type 2 diabetes. |
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| Keywords: | Lipoprotein lipase activator Pioglitazone Body weight gain Insulin resistance |
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