Sex Differences in Liver, Adipose Tissue, and Muscle Transcriptional Response to Fasting and Refeeding in Mice
Sex Differences in Liver, Adipose Tissue, and Muscle Transcriptional Response to Fasting and Refeeding in Mice
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DOI：
10.3390/cells8121529
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发表时间：
2019-12-01
期刊：
影响因子：
6
通讯作者：
Makarova, Elena
中科院分区：
文献类型：
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作者：
Bazhan, Nadezhda;Jakovleva, Tatiana;Makarova, Elena
禁食通常用于肥胖矫正，但“再进食综合征”限制了其效率，并且对不同食物供应的代谢反应的分子机制正在研究中。研究表明，性行为会影响荷尔蒙和对禁食/再进食的代谢反应。本研究的目的是评估雄性和雌性C57Bl/6J小鼠对禁食和再喂养的激素和转录反应。在激素和转录水平上都观察到性别不对称。禁食（24 h）诱导肝脏Fgf21基因表达增加，这与血浆Fgf21和脂联素水平升高以及参与脂肪酸氧化的肝脏（Ppar α、Cpt1 α）和肌肉（Cpt1 β、Ucp3）基因表达上调有关。这些变化在女性中更为明显。再饲喂（6 h）仅在雄性中引起高胰岛素血症和肝脏脂肪生成相关基因（Fasn）表达增加，仅在雌性中引起高瘦素血症和肌肉和脂肪组织中Fgf21基因表达增加。结果表明，小鼠禁食期间肝脏Ppar α、Cpt1 α、肌肉Cpt1 β和Ucp3表达性别不对称的分子机制之一是肝脏Fgf21的表达，而再喂养期间肝脏Fasn表达性别不对称的原因是雄性特异性高胰岛素血症。
Fasting is often used for obesity correction but the "refeeding syndrome" limits its efficiency, and molecular mechanisms underlying metabolic response to different food availability are under investigation. Sex was shown to affect hormonal and metabolic reactions to fasting/refeeding. The aim of this study was to evaluate hormonal and transcriptional responses to fasting and refeeding in male and female C57Bl/6J mice. Sex asymmetry was observed both at the hormonal and transcriptional levels. Fasting (24 h) induced increase in hepatic Fgf21 gene expression, which was associated with elevation of plasma FGF21 and adiponectin levels, and the upregulation of expression of hepatic (Ppar alpha, Cpt1 alpha) and muscle (Cpt1 beta, Ucp3) genes involved in fatty acid oxidation. These changes were more pronounced in females. Refeeding (6 h) evoked hyperinsulinemia and increased hepatic expression of gene related to lipogenesis (Fasn) only in males and hyperleptinemia and increase in Fgf21 gene expression in muscles and adipose tissues only in females. The results suggest that in mice, one of the molecular mechanisms underlying sex asymmetry in hepatic Ppar alpha, Cpt1 alpha, muscle Cpt1 beta, and Ucp3 expression during fasting is hepatic Fgf21 expression, and the reason for sex asymmetry in hepatic Fasn expression during refeeding is male-specific hyperinsulinemia.