Glucocorticoid/Adiponectin Axis Mediates Full Activation of Cold-Induced Beige Fat Thermogenesis.
Glucocorticoid/Adiponectin Axis Mediates Full Activation of Cold-Induced Beige Fat Thermogenesis.
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DOI：
10.3390/biom11111573
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发表时间：
2021-10-23
期刊：
影响因子：
5.5
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Luo L;Wang L;Luo Y;Romero E;Yang X;Liu M
糖皮质激素(GCs)是一类由肾上腺皮质在应激状态下产生的皮质类固醇，具有促进肥胖的作用。虽然适应性产热已被认为是对抗肥胖的有效方法，但GC是否在调节冷应激诱导的产热中发挥作用仍不完全清楚。在这里，我们发现，在冷暴露后48小时，啮齿动物循环中应激激素皮质酮(GC)的水平显著升高，而脂联素(一种与冷诱导的适应性产热有关的脂肪因子)的水平则下降。糖皮质激素氢化可的松的使用下调了Wat和白色脂肪细胞中的脂联素蛋白和mRNA水平，并上调了腹股沟脂肪中的生热基因的表达。相比之下，糖皮质激素受体拮抗剂米非司酮可以促进脂联素的表达，抑制体内的能量消耗。氢化可的松通过拮抗PPARγ在分化的3T3-L1脂肪细胞中抑制脂联素的表达。最终，脂联素缺乏恢复了米非司酮减少的耗氧量，并抑制了腹股沟脂肪中产热基因的表达。综上所述，我们的研究表明，GCS/脂联素轴是米色脂肪对急性冷应激反应的关键调控因素。
Glucocorticoids (GCs), a class of corticosteroids produced by the adrenal cortex in response to stress, exert obesity-promoting effects. Although adaptive thermogenesis has been considered an effective approach to counteract obesity, whether GCs play a role in regulating cold stress-induced thermogenesis remains incompletely understood. Here, we show that the circulating levels of stress hormone corticosterone (GC in rodents) were significantly elevated, whereas the levels of adiponectin, an adipokine that was linked to cold-induced adaptive thermogenesis, were decreased 48 h post cold exposure. The administration of a glucocorticoid hydrocortisone downregulated adiponectin protein and mRNA levels in both WAT and white adipocytes, and upregulated thermogenic gene expression in inguinal fat. In contrast, mifepristone, a glucocorticoid receptor antagonist, enhanced adiponectin expression and suppressed energy expenditure in vivo. Mechanistically, hydrocortisone suppressed adiponectin expression by antagonizing PPARγ in differentiated 3T3-L1 adipocytes. Ultimately, adiponectin deficiency restored mifepristone-decreased oxygen consumption and suppressed the expression of thermogenic genes in inguinal fat. Taken together, our study reveals that the GCs/adiponectin axis is a key regulator of beige fat thermogenesis in response to acute cold stress.
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影响因子：
82.9
作者：
Fischer K;Ruiz HH;Jhun K;Finan B;Oberlin DJ;van der Heide V;Kalinovich AV;Petrovic N;Wolf Y;Clemmensen C;Shin AC;Divanovic S;Brombacher F;Glasmacher E;Keipert S;Jastroch M;Nagler J;Schramm KW;Medrikova D;Collden G;Woods SC;Herzig S;Homann D;Jung S;Nedergaard J;Cannon B;Tschöp MH;Müller TD;Buettner C
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FELDMAN, D;HIRST, M
通讯作者：
HIRST, M
影响因子：
29
作者：
Holland WL;Adams AC;Brozinick JT;Bui HH;Miyauchi Y;Kusminski CM;Bauer SM;Wade M;Singhal E;Cheng CC;Volk K;Kuo MS;Gordillo R;Kharitonenkov A;Scherer PE
通讯作者：
Scherer PE
影响因子：
29
作者：
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通讯作者：
Cohen, Paul