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Diet-induced obesity suppresses cortical bone accrual by a neuropeptide Y-dependent mechanism

International Journal of Obesity volume 42, pages 1925–1938 (2018)Cite this article

Subjects

Abstract

Objective

To determine whether age and neuropeptide Y (NPY) were involved in the skeletal response to extended periods of diet-induced obesity.

Methods

Male wild-type (WT) and NPY null (NPYKO) mice were fed a mild (23% fat) high-fat diet for 10 weeks from 6 or 16 weeks of age. Metabolism and bone density were assessed during feeding. Skeletal changes were assessed by microCT and histomorphometry.

Results

High-fat feeding in 6-week-old WT mice led to significantly increased body weight, adiposity and serum leptin levels, accompanied with markedly suppressed cortical bone accrual. NPYKO mice were less susceptible to fat accrual but, importantly, displayed a complete lack of suppression of bone accrual or cortical bone loss. In contrast, when skeletally mature (16 week old) mice underwent 10 weeks of fat feeding, the metabolic response to HFD was similar to younger mice, however bone mass was not affected in either WT or NPYKO. Thus, growing mice are particularly susceptible to the detrimental effects of HFD on bone mass, through suppression of bone accrual involving NPY signalling.

Conclusion

This study provides new insights into the relationship between the opposing processes of a positive weight/bone relationship and the negative ‘metabolic’ effect of obesity on bone mass. This negative effect is particularly active in growing skeletons, which have heightened sensitivity to changes in obesity. In addition, NPY is identified as a fundamental driver of this negative ‘metabolic’ pathway to bone.

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Acknowledgements

NW was supported by an Australian Postgraduate Award (APA) administered by UNSW Australia. We would also like to thank the Biological Testing Facility at the Garvan Institute for assistance with the animal work.

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Authors and Affiliations

  1. Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia

    Natalie K. Y. Wee, Ronaldo F. Enriquez, Harry Horsnell, Rishikesh Kulkarni, Ee Cheng Khor & Paul A. Baldock

  2. Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia

    Amy D. Nguyen & Herbert Herzog

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Wee, N.K.Y., Enriquez, R.F., Nguyen, A.D. et al. Diet-induced obesity suppresses cortical bone accrual by a neuropeptide Y-dependent mechanism. Int J Obes 42, 1925–1938 (2018). https://doi.org/10.1038/s41366-018-0028-y

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