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

Carmen Huesa; Dongxing Zhu; James D Glover; Mathieu Ferron; Gerard Karsenty; Elspeth M Milne; José Luis Millan; S Faisal Ahmed; Colin Farquharson; Nicholas M Morton; Vicky E MacRae

doi:10.1242/dmm.017905

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

Carmen Huesa, Dongxing Zhu^*, James D Glover, Mathieu Ferron, Gerard Karsenty, Elspeth M Milne, José Luis Millan, S Faisal Ahmed, Colin Farquharson, Nicholas M Morton, Vicky E MacRae

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 is elevated in dermal fibroblast cultures and muscle of patients with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the NPP1 gene (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 sensitising bone-derived hormone osteocalcin but unchanged insulin signaling within osteoblasts. A fuller understanding of the pathways of NPP1 may inform the development of novel therapeutic strategies for treating insulin resistance.

Original language	English
Pages (from-to)	1341-1350
Number of pages	10
Journal	Disease Models and Mechanisms
Volume	7
Issue number	12
DOIs	https://doi.org/10.1242/dmm.017905
Publication status	Published - 31 Oct 2014

Keywords / Materials (for Non-textual outputs)

Mineralization
Obesity
Diabetes
MEMBRANE GLYCOPROTEIN PC-1
INSULIN-RESISTANCE
PYROPHOSPHATASE PHOSPHODIESTERASE-1
K121Q POLYMORPHISM
ENERGY-METABOLISM
GENE-EXPRESSION
ADIPOSE-TISSUE
IN-VITRO
INORGANIC PYROPHOSPHATE
ENPP1 GENE

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Characterising novel mediators of vascular calcification
MacRae, V.
BBSRC
1/01/09 → 31/01/16
Project: Research

Vicky MacRae
- vicky.macraeroslin.ed.acuk
- Royal (Dick) School of Veterinary Studies - Reader
Person: Academic: Research Active

Cite this

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title = "Deficiency of the bone mineralization inhibitor NPP1 protects against obesity and diabetes",

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 is elevated in dermal fibroblast cultures and muscle of patients with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the NPP1 gene (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 sensitising bone-derived hormone osteocalcin but unchanged insulin signaling within osteoblasts. A fuller understanding of the pathways of NPP1 may inform the development of novel therapeutic strategies for treating insulin resistance.",

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author = "Carmen Huesa and Dongxing Zhu and Glover, {James D} and Mathieu Ferron and Gerard Karsenty and Milne, {Elspeth M} and Millan, {Jos{\'e} Luis} and Ahmed, {S Faisal} and Colin Farquharson and Morton, {Nicholas M} and MacRae, {Vicky E}",

year = "2014",

month = oct,

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doi = "10.1242/dmm.017905",

language = "English",

volume = "7",

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AU - Karsenty, Gerard

AU - Milne, Elspeth M

AU - Millan, José Luis

AU - Ahmed, S Faisal

AU - Farquharson, Colin

AU - Morton, Nicholas M

AU - MacRae, Vicky E

PY - 2014/10/31

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AB - 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 is elevated in dermal fibroblast cultures and muscle of patients with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the NPP1 gene (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 sensitising bone-derived hormone osteocalcin but unchanged insulin signaling within osteoblasts. A fuller understanding of the pathways of NPP1 may inform the development of novel therapeutic strategies for treating insulin resistance.

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KW - INSULIN-RESISTANCE

KW - PYROPHOSPHATASE PHOSPHODIESTERASE-1

KW - K121Q POLYMORPHISM

KW - ENERGY-METABOLISM

KW - GENE-EXPRESSION

KW - ADIPOSE-TISSUE

KW - IN-VITRO

KW - INORGANIC PYROPHOSPHATE

KW - ENPP1 GENE

U2 - 10.1242/dmm.017905

DO - 10.1242/dmm.017905

M3 - Article

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SN - 1754-8411

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JO - Disease Models and Mechanisms

JF - Disease Models and Mechanisms

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ER -

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

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Keywords / Materials (for Non-textual outputs)

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