Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity.
Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity.
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DOI：
10.1016/j.isci.2021.103448
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发表时间：
2021-12-17
期刊：
影响因子：
5.8
通讯作者：
Oyadomari S
中科院分区：
文献类型：
--
作者：
Miyake M;Zhang J;Yasue A;Hisanaga S;Tsugawa K;Sakaue H;Oyadomari M;Kiyonari H;Oyadomari S
eIF 2 α磷酸化依赖性整合应激反应（ISR）是一种维持哺乳动物细胞内稳态的信号通路。在这里，脂肪细胞中的ISR激活通过以非细胞自主的方式调节食欲来改善肥胖和糖尿病。使用转基因小鼠的脂肪细胞特异性ISR活化通过优先抑制高脂饮食（HFD）摄入来降低体重并改善由HFD诱导的葡萄糖耐量和肥胖。ISR激活的脂肪组织的转录组分析揭示，生长分化因子15（GDF 15）的表达由ISR通过直接调节转录因子ATF 4和DDIT 3诱导。GDF 15受体GFRAL的缺乏消除了HFD摄入的脂肪细胞ISR依赖性优先抑制和抗肥胖作用。在药理学上，10（E），12（Z）-十八碳二烯酸诱导脂肪细胞中ISR依赖性GDF 15表达并减少HFD的摄入。根据我们的研究结果，脂肪细胞中ISR的特异性激活控制着食欲的非细胞自主调节。脂肪细胞中ISR的激活抑制高脂饮食的摄入并防止肥胖由ISR诱导的ATF 4和DDIT 3直接调节GDF 15表达GDF 15-GFRAL轴通过ISR激活介导对高脂饮食的食欲的控制一种共轭亚油酸诱导脂肪细胞中ISR和GDF 15的表达生物科学;人体代谢;细胞生物学
The eIF2α phosphorylation-dependent integrated stress response (ISR) is a signaling pathway that maintains homeostasis in mammalian cells exposed to various stresses. Here, ISR activation in adipocytes improves obesity and diabetes by regulating appetite in a non-cell-autonomous manner. Adipocyte-specific ISR activation using transgenic mice decreases body weight and improves glucose tolerance and obesity induced by a high-fat diet (HFD) via preferential inhibition of HFD intake. The transcriptome analysis of ISR-activated adipose tissue reveals that growth differentiation factor 15 (GDF15) expression is induced by the ISR through the direct regulation of the transcription factors ATF4 and DDIT3. Deficiency in the GDF15 receptor GFRAL abolishes the adipocyte ISR-dependent preferential inhibition of HFD intake and the anti-obesity effects. Pharmacologically, 10(E), 12(Z)-octadecadienoic acid induces ISR-dependent GDF15 expression in adipocytes and decreases the intake of the HFD. Based on our findings the specific activation of the ISR in adipocytes controls the non-cell-autonomous regulation of appetite. Activation of ISR in adipocytes suppresses intake of high-fat diet and prevents obesity ATF4 and DDIT3 induced by ISR directly regulate GDF15 expression GDF15-GFRAL axis mediates the control of appetite for high-fat diet by ISR activation One of conjugated linoleic acids induces ISR and GDF15 expression in adipocytes Biological sciences; Human metabolism; Cell biology
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影响因子：
82.9
作者：
Emmerson, Paul J.;Wang, Feng;Wu, Xinle
通讯作者：
Wu, Xinle
DOI：
10.1126/science.aaa4484
发表时间：
2015-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Das I;Krzyzosiak A;Schneider K;Wrabetz L;D'Antonio M;Barry N;Sigurdardottir A;Bertolotti A
通讯作者：
Bertolotti A
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
16.6
作者：
Jung SB;Choi MJ;Ryu D;Yi HS;Lee SE;Chang JY;Chung HK;Kim YK;Kang SG;Lee JH;Kim KS;Kim HJ;Kim CS;Lee CH;Williams RW;Kim H;Lee HK;Auwerx J;Shong M
通讯作者：
Shong M
影响因子：
64.5
作者：
Nakamura T;Furuhashi M;Li P;Cao H;Tuncman G;Sonenberg N;Gorgun CZ;Hotamisligil GS
通讯作者：
Hotamisligil GS