Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding
Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding
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DOI：
10.1007/s00125-013-2846-8
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发表时间：
2013-05-01
期刊：
影响因子：
8.2
通讯作者：
Turner, N.
中科院分区：
文献类型：
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作者：
Montgomery, M. K.;Hallahan, N. L.;Turner, N.
AIMS/假说代谢紊乱通常使用基因敲除和转基因小鼠模型进行研究。为此，已经使用了各种小鼠品系。然而，小鼠品系发生代谢性疾病的内在倾向可能不同，这可能会影响代谢研究的实验结果。我们研究了5个常用近交系小鼠(C57BL/6J、129X1/SVJ、BALB/c、DBA/2和FVB/N)对饮食性肥胖和胰岛素抵抗的易感性的品系差异。然后测定全身能量消耗和身体成分。结果BL6、129X1、DBA/2和FVB/N小鼠均不同程度地易受HFD诱导的肥胖、糖耐量异常和胰岛素抵抗的影响，但BALB/c小鼠对这些有害影响有一定的保护作用。这种保护不能用线粒体新陈代谢的差异、肝脏或肌肉的氧化应激或脂肪组织的炎症来解释。有趣的是，与其他品系相比，BALB/c小鼠没有在肝脏中积累过多的脂肪(三酰甘油和二酰甘油)；这可能与较低的脂肪酸摄取有关，而不是脂肪生成或脂质氧化的差异。结论/综合解释，我们的发现表明，大多数品系的小鼠在HFD上出现代谢缺陷。然而，菌株之间存在固有的差异，因此在新陈代谢研究中需要仔细考虑遗传背景。
Aims/hypothesis Metabolic disorders are commonly investigated using knockout and transgenic mouse models. A variety of mouse strains have been used for this purpose. However, mouse strains can differ in their inherent propensities to develop metabolic disease, which may affect the experimental outcomes of metabolic studies. We have investigated strain-dependent differences in the susceptibility to diet-induced obesity and insulin resistance in five commonly used inbred mouse strains (C57BL/6J, 129X1/SvJ, BALB/c, DBA/2 and FVB/N).Methods Mice were fed either a low-fat or a high-fat diet (HFD) for 8 weeks. Whole-body energy expenditure and body composition were then determined. Tissues were used to measure markers of mitochondrial metabolism, inflammation, oxidative stress and lipid accumulation.Results BL6, 129X1, DBA/2 and FVB/N mice were all susceptible to varying degrees to HFD-induced obesity, glucose intolerance and insulin resistance, but BALB/c mice exhibited some protection from these detrimental effects. This protection could not be explained by differences in mitochondrial metabolism or oxidative stress in liver or muscle, or inflammation in adipose tissue. Interestingly, in contrast with the other strains, BALB/c mice did not accumulate excess lipid (triacylglycerols and diacylglycerols) in the liver; this is potentially related to lower fatty acid uptake rather than differences in lipogenesis or lipid oxidation.Conclusions/interpretation Collectively, our findings indicate that most mouse strains develop metabolic defects on an HFD. However, there are inherent differences between strains, and thus the genetic background needs to be considered carefully in metabolic studies.