Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes.
Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes.
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DOI：
10.1242/dmm.017905
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发表时间：
2014-12
影响因子：
4.3
通讯作者：
MacRae VE
中科院分区：
文献类型：
--
作者：
Huesa C;Zhu D;Glover JD;Ferron M;Karsenty G;Milne EM;Millan JL;Ahmed SF;Farquharson C;Morton NM;MacRae VE
骨作为内分泌调节因子的出现促使人们重新评估骨矿化因子在代谢性疾病发展中的作用。外核苷酸焦磷酸酶/磷酸二酯酶-1 （NPP1）通过焦磷酸盐的生成控制骨矿化，在胰岛素抵抗个体的真皮成纤维细胞培养和肌肉中，NPP1的水平升高。我们研究了缺乏编码NPP1基因的小鼠（Enpp1 - / -小鼠）与骨代谢受损相关的代谢表型。Enpp1−/−小鼠在正常饮食下表现出轻度改善的葡萄糖稳态，但在长期高脂肪喂养下表现出明显的肥胖抵抗和胰岛素抵抗。Enpp1−/−小鼠的胰岛素致敏骨源性激素骨钙素水平升高，但成骨细胞内的胰岛素信号传导不变。更全面地了解NPP1的通路可以为治疗胰岛素抵抗的新治疗策略的发展提供信息。
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.
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影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
3.7
作者：
Di Paola R;Caporarello N;Marucci A;Dimatteo C;Iadicicco C;Del Guerra S;Prudente S;Sudano D;Miele C;Parrino C;Piro S;Beguinot F;Marchetti P;Trischitta V;Frittitta L
通讯作者：
Frittitta L
影响因子：
6
作者：
Anderson, HC;Harmey, D;Millán, JL
通讯作者：
Millán, JL
影响因子：
6.2
作者：
Johnson, K;Goding, J;Terkeltaub, R
通讯作者：
Terkeltaub, R
影响因子：
64.5
作者：
Lee, Na Kyung;Sowa, Hideaki;Karsenty, Gerard
通讯作者：
Karsenty, Gerard