Diet-induced obesity in two C57BL/6 substrains with intact or mutant nicotinamide nucleotide transhydrogenase (Nnt) gene.
Diet-induced obesity in two C57BL/6 substrains with intact or mutant nicotinamide nucleotide transhydrogenase (Nnt) gene.
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DOI：
10.1038/oby.2009.477
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发表时间：
2010-10
期刊：
影响因子：
6.9
通讯作者：
Leiter, Edward H.
中科院分区：
文献类型：
--
作者：
Nicholson, Anthony;Reifsnyder, Peter C.;Malcolm, Rachel D.;Lucas, Charlotte A.;MacGregor, Grant R.;Zhang, Weidong;Leiter, Edward H.
C57 BL/6 J（B6/J）雄性小鼠代表了饮食诱导肥胖（DIO）的标准，并且在表达功能丧失型烟酰胺核苷酸转氢酶（Nnt）基因方面是独特的。这种突变与体外B6/J胰岛葡萄糖刺激的胰岛素分泌显著减少和体内葡萄糖清除中度受损有关。为了评估这种Nnt突变的贡献，我们在14周的高脂肪（60%的卡路里）饮食喂养期间比较了Nnt突变型B6/J雄性与Nnt野生型C57 BL/6 NJ（B6/NJ）雄性的DIO响应性。6周时的初始平均体重未区分亚株，两种亚株均对DIO敏感。然而，B6/J雄性动物的增重超过B6/NJ雄性动物，20周时平均体重显著增加3g，同时瘦体重和脂肪量显著增加。随着时间的推移，B6/J雄性动物的平均非空腹血糖也显著较高，8周龄和20周龄时评估的葡萄糖耐量受损也是如此。血清瘦素，但不是胰岛素，显着较高的B6/J男性随着时间的推移。野生型Nnt基因的潜在贡献在低脂肪饮食（10%的卡路里）中得到证实，其中B6/NJ雄性随时间推移的显著更大的体重增加与显著更高的血清胰岛素相关。总之，无论Nnt等位基因状态如何，DIO都是对60%脂肪喂养的反应。与B6/NJ雄性相比，B6/J独特Nnt突变的贡献在对10%脂肪喂养的反应中最为明显，导致血清胰岛素和体重增加减少。
The C57BL/6J (B6/J) male mouse represents a standard for diet induced obesity (DIO) and is unique in expressing a loss-of-function Nicotinamide Nucleotide Transhydrogenase (Nnt) gene. This mutation was associated with a marked reduction in glucose-stimulated insulin secretion from B6/J islets in vitro and moderately impaired glucose clearance in vivo. To assess the contribution of this Nnt mutation, we compared DIO responsiveness of Nnt-mutant B6/J males to Nnt wildtype C57BL/6NJ (B6/NJ) males over a 14 week period of feeding a high fat (60% of calories) diet. Initial mean body weights at 6 weeks did not distinguish the substrains and both substrains were DIO sensitive. However, B6/J males outgained the B6/NJ males, with a significant 3g higher mean body weight at 20 weeks accompanied by significant increases in both lean and fat mass. Mean non-fasting serum glucose over time was also significantly higher in B6/J males, as was impairment of glucose tolerance assessed at 8 and 20 weeks of age. Serum leptin, but not insulin, was significantly higher in B6/J males over time. Potential contributions of the wildtype Nnt gene were demonstrable on a lower fat diet (10% of calories) where a significantly greater weight gain over time by B6/NJ males was correlated with a significantly higher serum insulin. In conclusion, DIO developed in response to 60% fat feeding regardless of Nnt allele status. Contribution of the B6/J-unique Nnt mutation was most evident in response to 10% fat feeding that resulted in reduced serum insulin and weight gain compared to B6/NJ males.
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影响因子：
2.5
作者：
Mulligan, M. K.;Ponomarev, I.;Bergeson, S. E.
通讯作者：
Bergeson, S. E.
影响因子：
29
作者：
Freeman, H;Shimomura, K;Ashcroft, FM
通讯作者：
Ashcroft, FM
影响因子：
8.2
作者：
Aston-Mourney, K.;Wong, N.;Andrikopoulos, S.
通讯作者：
Andrikopoulos, S.
影响因子：
8.2
作者：
Toye, AA;Lippiat, JD;Cox, RD
通讯作者：
Cox, RD
DOI：
10.1016/0167-5699(82)90093-7
发表时间：
1982-01-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
BAILEY, DW
通讯作者：
BAILEY, DW