Flattening of diurnal glucocorticoid oscillations causes Cd36 and insulin-mediated obesity

Flattening of diurnal glucocorticoid oscillations causes Cd36 and insulin-mediated obesity
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昼夜糖皮质激素振荡变平导致 Cd36 和胰岛素介导的肥胖

DOI:
10.1101/2020.01.02.893081
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发表时间:
--
期刊:
bioRxiv
影响因子:
--
通讯作者:
Teruel M.
Teruel M.
中科院分区:
--
文献类型:
--
作者:
Tholen S;Teruel M.

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慢性压力源会抑制每日糖皮质激素的波动,导致肥胖、胰岛素抵抗和糖尿病。这种平缓的昼夜糖皮质激素振荡如何增加脂肪储存尚不清楚。在这里,我们研究了小鼠的后果,发现糖皮质激素振荡的平缓不仅会导致体重增加(主要是由于白色脂肪库质量的增加),还会导致高胰岛素血症和棕色脂肪组织中的脂肪堆积。对白色和棕色脂肪组织的转录组分析表明,扁平的糖皮质激素振荡会导致脂质代谢失调,其中脂肪酸转运蛋白 Cd36 和胰岛素驱动的脂肪细胞肥大发挥着重要作用。事实上,Cd36 敲除小鼠可以部分免受GC振荡平坦化的不利影响,包括体重增加以及棕色和内脏白色脂肪库中的脂质积累。这些结果显示了糖皮质激素振荡平缓如何导致肥胖和糖尿病的分子机制。
Chronic stressors flatten diurnal glucocorticoid oscillations, resulting in obesity, insulin resistance, and diabetes. How such flattened diurnal glucocorticoid oscillations increase fat storage is unknown. Here we investigated the consequences in mice and found that flattening of glucocorticoid oscillations results not only in body weight gain, mainly due to increases in white fat depot mass, but also leads to hyperinsulinemia and fat accumulation in brown adipose tissue. A transcriptomic analysis of white and brown adipose tissues revealed that flattened glucocorticoid oscillations cause dysregulated lipid metabolism with a prominent role of the fatty acid transporter Cd36 and insulin-driven adipocyte hypertrophy. Indeed, Cd36 knockout mice are partially protected against the adverse effects of flattened GC oscillations including body weight gain and lipid accumulation in the brown and visceral white fat depots. These results show the molecular mechanisms how flattened glucocorticoid oscillations can cause obesity and diabetes.
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