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Acute effects of brain-derived neurotrophic factor on energy expenditure in obese diabetic mice

International Journal of Obesity volume 25, pages 1286–1293 (2001)Cite this article

Abstract

OBJECTIVE: We recently demonstrated that chronic treatment with brain-derived neurotrophic factor (BDNF) regulates energy expenditure in obese diabetic C57BL/KsJ-db/db mice. In this study, we investigated the acute effects of BDNF on energy expenditure.

DESIGN: After BDNF was singly administered to male db/db mice (aged 10–12 weeks), their body temperature and whole body glucose oxidation were measured. Their norepinephrine (NE) turnover and uncoupling protein (UCP) 1 expression in interscapular brown adipose tissue (BAT) were also analyzed.

RESULTS: Even though the body temperatures of hyperphagic db/db mice dropped remarkably in a 24 h period after food deprivation, only a single subcutaneous administration of BDNF significantly prevented the reduction of body temperature. BDNF was also observed to have similar efficacy in cold exposure experiments at 15°C. Respiratory excretion of 14CO2 after intravenous injection of D-[14C(U)]-glucose was significantly increased by BDNF administration, indicating that BDNF increases whole-body glucose oxidation. BDNF administered intracerebroventricularly was also able to prevent the reduction of body temperature of db/db mice. To clarify the BDNF action mechanism we examined NE turnover in BAT. Four hours after a single administration, BDNF reduced NE content in the presence of the tyrosine hydroxylase inhibitor, α-methyl-P-tyrosine methyl ester, indicating enhanced NE turnover in BAT. BDNF also increased the expression of the UCP1 mRNA and protein in BAT.

CONCLUSION: These data indicate that BDNF rapidly regulates energy metabolism in obese diabetic animals, partly through activating the sympathetic nervous system and inducing UCP1 gene expression in BAT.

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Acknowledgements

The authors thank Mr Masayuki Satoh (Sumitomo Chemical, Osaka, Japan) for conducting the glucose oxidation analysis. This study was supported by Sumitomo Pharmaceuticals Co. Ltd, Osaka, Japan.

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Authors and Affiliations

  1. Sumitomo Pharmaceuticals Co. Ltd, Discovery Research Laboratories II, Osaka, Japan

    A Tsuchida, T Nonomura, M Ono-Kishino, T Nakagawa, M Taiji & H Noguchi

  2. Sumitomo Pharmaceuticals Co. Ltd, Business Development and Licensing Office, Tokyo, Japan

    H Noguchi

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  1. A Tsuchida
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  2. T Nonomura
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  3. M Ono-Kishino
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  4. T Nakagawa
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  5. M Taiji
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Correspondence to M Taiji.

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Tsuchida, A., Nonomura, T., Ono-Kishino, M. et al. Acute effects of brain-derived neurotrophic factor on energy expenditure in obese diabetic mice. Int J Obes 25, 1286–1293 (2001). https://doi.org/10.1038/sj.ijo.0801678

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