The metabolic response to a high-fat diet reveals obesity-prone and -resistant phenotypes in mice with distinct mRNA-seq transcriptome profiles
The metabolic response to a high-fat diet reveals obesity-prone and -resistant phenotypes in mice with distinct mRNA-seq transcriptome profiles
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DOI：
10.1038/ijo.2016.70
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发表时间：
2016-09-01
影响因子：
4.9
通讯作者：
Choi, M-S
中科院分区：
文献类型：
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作者：
Choi, J-Y;McGregor, R. A.;Choi, M-S
目的：基于高脂饮食(HFD)对C57BL/6J小鼠代谢和转录水平的影响，探讨肥胖易感性或抵抗的表型差异。6周后，根据体重增加情况，将服用HFD的小鼠分为肥胖易感(OP)组和肥胖抵抗(OR)组。结果：OR组小鼠的血浆和肝脏血脂水平较OP组显著改善。OR组小鼠的能量消耗大于OP组小鼠，同时体内脂肪质量也减少。OP组小鼠附睾部白色脂肪组织(EWAT)和肝脏明显增大(有明显的免疫细胞浸润)，而OR组上述作用较OP组小鼠减弱。与OP鼠相比，OR鼠的整体糖代谢增强，包括对胰岛素抵抗、血糖和胰岛素浓度、葡萄糖激酶活性和肝糖原的稳态模型评估。OP组小鼠血浆脂肪因子和促炎细胞因子表达上调，而OR组这些变化明显减弱。EWAT和肝脏的转录图谱显示了OP和OR小鼠共同的和不同的转录变化模式，并表明OP和OR小鼠的不同代谢表型。OP和OR小鼠在动脉粥样硬化信号转导、精子活力、eWAT中cAMP介导的信号转导、肝脏纤维化、颗粒细胞黏附和分裂以及动脉粥样硬化信号转导等分子通路上存在显著差异。结论：综上所述，本研究结果为高脂饲料喂养的C57BL/6J小鼠肥胖易感性和肥胖抵抗之间的转录本、表型和代谢过程的重大差异提供了强有力的证据。
OBJECTIVES: The aim of this study was to explore the phenotypic differences underpinning obesity susceptibility or resistance based on the metabolic and transcriptional profiling of C57BL/6J mice fed a high-fat diet (HFD).METHODS: The mice were fed either a normal diet or HFD for 12 weeks. After 6 weeks, the mice on HFD were classified as either obesity-prone (OP) or obesity-resistant (OR) depending on the body weight gain.RESULTS: Lipid profiles from plasma and liver significantly improved in OR mice relative to the OP group. Energy expenditure was greater in OR mice than in OP mice, with a simultaneous decrease in body fat mass. Epididymal white adipose tissue (eWAT) and liver were enlarged in OP mice (with visible immune-cell infiltration), but these effects were attenuated in OR mice compared with OP mice. Overall glucose metabolism was enhanced in OR mice compared with OP mice, including homeostasis model assessment for insulin resistance, plasma glucose and insulin concentrations, glucokinase activity and hepatic glycogen. Plasma adipokines and proinflammatory cytokines were upregulated in OP mice, and these changes were attenuated in OR mice. Transcriptomic profiles of eWAT and liver revealed common and divergent patterns of transcriptional changes in OP and OR mice, and pointed to differential metabolic phenotypes of OP and OR mice. There were substantial differences between OP and OR mice in molecular pathways, including atherosclerosis signaling, sperm motility, cAMP-mediated signaling in eWAT; and fibrosis, agranulocyte adhesion and diapedesis, and atherosclerosis signaling in liver.CONCLUSIONS: Taken altogether, the results provide robust evidence of major divergence in the transcriptomes, phenotypes and metabolic processes between obesity susceptibility and obesity resistance in the HFD-fed C57BL/6J mice.