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Antiobesity and antidiabetic effects of brain-derived neurotrophic factor in rodent models of leptin resistance

International Journal of Obesity volume 27, pages 557–565 (2003)Cite this article

Abstract

OBJECTIVE: Obesity in rodents and humans is mostly associated with elevated plasma leptin concentrations, suggesting a new pathological concept of ‘leptin resistance’. We have demonstrated that brain-derived neurotrophic factor (BDNF) can improve obesity and diabetes of C57BL/KsJ db/db (db/db) mice. In this study, we investigated whether or not BDNF is effective in two different models of leptin resistance, an acquired model and a genetic model.

DESIGN: C57BL/6J mice rendered obese by consumption of a high-fat diet (diet-induced obesity (DIO) mice) were used as an acquired model and lethal yellow agouti mice (KKAy mice) as a genetic model of leptin resistance. Food intake and glucose metabolism were studied after acute or repetitive administration of BDNF.

RESULTS:Intraperitoneal administration of BDNF (10 mg/kg, twice/day) significantly reduced cumulative food intake of DIO and KKAy mice, whereas they were unresponsive to leptin administration. Repetitive subcutaneous administration of BDNF (10 mg/kg daily for 6 days) reduced food intake and improved impaired glucose tolerance in DIO mice. Pair feeding of vehicle-treated DIO mice with the same amount of chow consumed by the BDNF-treated group did not improve the impaired glucose homeostasis, indicating that the antidiabetic effect is not due to decreased food intake. We also observed that BDNF is effective in improving obesity and diabetes of KKAy mice.

CONCLUSION:This study demonstrated antiobesity and antidiabetic effects of BDNF in two different models of leptin resistance, thereby suggesting the therapeutic potential of BDNF in the treatment of leptin-resistant obesity and diabetes.

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Acknowledgements

We thank S Hidaka and M Shintani for valuable discussions. This work is supported in part by research grants from the Japanese Ministry of Education, Science, Sports and Culture, and the Japanese Ministry of Health and Welfare.

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Authors and Affiliations

  1. Sumitomo Pharmaceuticals Research Division, Discovery Research Laboratories'I, Osaka, 554-0022, Japan

    T Nakagawa, M Yamanaka, A Tsuchida & M Taiji

  2. Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan

    Y Ogawa, K Ebihara & K Nakao

  3. Sumitomo Pharmaceuticals Business Development and Licensing Office, Tokyo, 101-8319, Japan

    H Noguchi

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Correspondence to Y Ogawa.

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Nakagawa, T., Ogawa, Y., Ebihara, K. et al. Antiobesity and antidiabetic effects of brain-derived neurotrophic factor in rodent models of leptin resistance. Int J Obes 27, 557–565 (2003). https://doi.org/10.1038/sj.ijo.0802265

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