A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice.
A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice.
复制标题
作者：
Fisher-Wellman KH;Ryan TE;Smith CD;Gilliam LA;Lin CT;Reese LR;Torres MJ;Neufer PD
虽然已知烟酰胺核苷酸转氢酶（NNT）缺陷型C57 BL/6 J（6 J）小鼠对饮食诱导的代谢疾病高度易感，但这一观点主要源于6 J小鼠与其他近交系小鼠的比较。迄今为止，很少有研究直接比较NNT缺陷型6 J小鼠和NNT活性C57 BL/6亚株之间的代谢疾病易感性。在这项研究中，在6 J和C57 BL/6 NJ（6 N）小鼠中，比较了对高脂肪/高蔗糖饮食（HFD）的代谢反应随时间变化的综合特征。鉴于过氧化物暴露增加会导致胰岛素抵抗，加上NNT调节过氧化物解毒的事实，假设6 J小鼠在HFD暴露后会经历氧化还原稳态/代谢疾病的更大紊乱。与此相反，这两个线被发现是高度敏感的饮食诱导的代谢疾病，证明了在葡萄糖耐量的损害，早在24小时进入HFD。此外，在6 J小鼠中，代谢综合征的各种标志物以及过氧化物应激实际上是钝化的，而不是加剧的，这可能反映了替代氧化还原缓冲途径的代偿性增加。总之，这些数据提供的证据表明，对HFD诱导的代谢性疾病的易感性在6 J和6 N亚株中是相似的。考虑到6 J染色中的许多遗传变异，包括NNT功能的丧失，这些发现表明6 N亚株是代谢研究中更合乎逻辑和代表性的遗传背景模型。
Although nicotinamide nucleotide transhydrogenase (NNT)–deficient C57BL/6J (6J) mice are known to be highly susceptible to diet-induced metabolic disease, this notion stems primarily from comparisons of 6J mice to other inbred strains. To date, very few studies have directly compared metabolic disease susceptibility between NNT-deficient 6J mice and NNT-competent C57BL/6 substrains. In this study, comprehensive profiling of the metabolic response to a high-fat/high-sucrose diet (HFD) were compared across time in 6J and C57BL/6NJ (6N) mice. Given that increased peroxide exposure drives insulin resistance, coupled with the fact that NNT regulates peroxide detoxification, it was hypothesized that 6J mice would experience greater derangements in redox homeostasis/metabolic disease upon HFD exposure. Contrary to this, both lines were found to be highly susceptible to diet-induced metabolic disease, as evidenced by impairments in glucose tolerance as early as 24 h into the HFD. Moreover, various markers of the metabolic syndrome, as well as peroxide stress, were actually blunted, rather than exacerbated, in the 6J mice, likely reflecting compensatory increases in alterative redox-buffering pathways. Together, these data provide evidence that the susceptibility to HFD-induced metabolic disease is similar in the 6J and 6N substrains. Given the numerous genetic variances in the 6J stain, including loss of NNT function, these findings suggest that the 6N substrain is the more logical and representative genetic background model for metabolic studies.
登录
查看更多内容
影响因子：
7
作者：
Go, Young-Mi;Roede, James R.;Jones, Dean P.
通讯作者：
Jones, Dean P.
影响因子：
14.8
作者：
Giustarini, Daniela;Dalle-Donne, Isabella;Rossi, Ranieri
通讯作者：
Rossi, Ranieri
DOI：
10.1073/pnas.0902380106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Hoehn, Kyle L.;Salmon, Adam B.;James, David E.
通讯作者：
James, David E.
影响因子：
15.9
作者：
Anderson, Ethan J.;Lustig, Mary E.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
影响因子：
7.4
作者：
Fisher-Wellman, Kelsey H.;Gilliam, Laura A. A.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell