Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes

Huesa, C. et al. (2014) Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes. Disease Models and Mechanisms, 7(12), pp. 1341-1350. (doi: 10.1242/dmm.017905)

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Abstract

The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the gene that encodes NPP1 (Enpp1−/− mice). Enpp1−/− mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high-fat feeding. Enpp1−/− mice had increased levels of the insulin-sensitizing bone-derived hormone osteocalcin but unchanged insulin signalling within osteoblasts. A fuller understanding of the pathways of NPP1 could inform the development of novel therapeutic strategies for treating insulin resistance.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ahmed, Professor Syed Faisal and Huesa, Dr Carmen
Authors: Huesa, C., Zhu, D., Glover, J. D., Ferron, M., Karsenty, G., Milne, E. M., Millan, J. L., Ahmed, S. F., Farquharson, C., Morton, N. M., and MacRae, V. E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Disease Models and Mechanisms
Publisher:The Company of Biologists Ltd.
ISSN:1754-8411
ISSN (Online):1754-8403
Copyright Holders:Copyright © 2014 The Company of Biologists Ltd.
First Published:First published in Disease Models and Mechanisms 7(12):1341-1350
Publisher Policy:Reproduced under a Creative Commons License
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