Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy.
Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy.
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DOI：
10.1016/j.celrep.2022.111018
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发表时间：
2022-06-28
期刊：
影响因子：
8.8
通讯作者：
Teruel, Mary N.
中科院分区：
文献类型：
--
作者：
Tholen, Stefan;Patel, Roma;Agas, Agnieszka;Kovary, Kyle M.;Rabiee, Atefeh;Nicholls, Hayley T.;Bielczyk-Maczynska, Ewa;Yang, Wenting;Kraemer, Fredric B.;Teruel, Mary N.
库欣病和慢性应激中昼夜糖皮质激素振荡的破坏导致肥胖和脂肪细胞肥大，这被认为是肥胖有害影响的主要来源。在这里，我们通过平抑小鼠的糖皮质激素波动来概括由于时差或工作与生活不平衡而引起的压力。在3天内，小鼠达到具有持续高胰岛素的代谢状态，但令人惊讶的是血液中葡萄糖和脂肪酸低，这在3周内棕色和白色脂肪组织质量增加超过2倍之前。转录组学和Cd36基因敲除小鼠分析表明，高胰岛素血症介导的从头脂肪酸合成和Cd36介导的脂肪酸摄取驱动脂肪量增加。有趣的是，糖皮质激素扁平化导致急性高胰岛素血症和脂肪细胞肥大的这种机制出乎意料地有利于防止高水平的循环脂肪酸和葡萄糖数周，从而作为一种保护性反应，以保持慢性应激期间的代谢健康。托伦等人表明，平缓的昼夜节律糖皮质激素通过急性高胰岛素血症驱动脂肪细胞肥大，这使循环脂肪酸和葡萄糖保持在低水平，并且在慢性应激期间出乎意料地保护代谢健康数周。
Disruption of circadian glucocorticoid oscillations in Cushing’s disease and chronic stress results in obesity and adipocyte hypertrophy, which is believed to be a main source of the harmful effects of obesity. Here, we recapitulate stress due to jet lag or work-life imbalances by flattening glucocorticoid oscillations in mice. Within 3 days, mice achieve a metabolic state with persistently high insulin, but surprisingly low glucose and fatty acids in the bloodstream, that precedes a more than 2-fold increase in brown and white adipose tissue mass within 3 weeks. Transcriptomic and Cd36-knockout mouse analyses show that hyperinsulinemia-mediated de novo fatty acid synthesis and Cd36-mediated fatty acid uptake drive fat mass increases. Intriguingly, this mechanism by which glucocorticoid flattening causes acute hyperinsulinemia and adipocyte hypertrophy is unexpectedly beneficial in preventing high levels of circulating fatty acids and glucose for weeks, thus serving as a protective response to preserve metabolic health during chronic stress. Tholen et al. show that flattening circadian glucocorticoids drives adipocyte hypertrophy via acute hyperinsulinemia, which keeps circulating fatty acids and glucose low and is unexpectedly protective to preserve metabolic health for weeks during chronic stress.
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.1900125116
发表时间：
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影响因子：
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作者：
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通讯作者：
FERTIG, JW
影响因子：
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作者：
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通讯作者：
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