The autophagy protein Becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding.
The autophagy protein Becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding.
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DOI：
10.1016/j.celrep.2021.109184
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发表时间：
2021-05-25
期刊：
影响因子：
8.8
通讯作者：
He C
中科院分区：
文献类型：
--
作者：
Kuramoto K;Kim YJ;Hong JH;He C
自噬失调与包括2型糖尿病在内的代谢性疾病有关。然而，自噬机制调节新陈代谢的机制在很大程度上还不清楚。自噬通常被认为是通过溶酶体的降解过程。在这里，我们揭示了一种代谢上重要的非细胞自主的、非降解的机制，该机制受脂肪组织中必需的自噬蛋白Becn1调节。在高脂饮食刺激下，自噬过度活跃的Becn1F121a小鼠表现出系统性的胰岛素敏感性改善，并通过脂联素(一种脂肪衍生的代谢激素)介导的非细胞自主机制，增强了AMP激活的蛋白激酶(AMPK)的激活，AMPK是能量稳态的中央调节因子。脂肪特异性Becn1F121a的表达足以激活非脂肪组织中的AMPK，并通过增加脂联素的分泌来改善全身胰岛素敏感性。此外，Becn1通过螺旋卷曲结构域与外囊复合体的成分相互作用，从而促进脂联素的分泌。总之，我们的研究表明，Becn1通过结合脂肪组织中的外囊来促进脂联素的分泌，从而改善胰岛素敏感性。Kuramoto et al.展示了一种非降解和非细胞自主的机制，自噬蛋白Becn1通过这种机制调节全身能量代谢。Becn1与白色脂肪组织中的外囊蛋白相互作用，促进脂联素的分泌，导致非脂肪组织中脂联素受体-AMPK信号通路的全身性胰岛素增敏。
Autophagy dysregulation is implicated in metabolic diseases, including type 2 diabetes. However, the mechanism by which the autophagy machinery regulates metabolism is largely unknown. Autophagy is generally considered a degradation process via lysosomes. Here, we unveil a metabolically important non-cell-autonomous, non-degradative mechanism regulated by the essential autophagy protein Becn1 in adipose tissue. Upon high-fat diet challenge, autophagy-hyperactive Becn1F121A mice show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell-autonomous mechanism mediated by adiponectin, an adipose-derived metabolic hormone. Adipose-specific Becn1F121A expression is sufficient to activate AMPK in non-adipose tissues and improve systemic insulin sensitivity by increasing adiponectin secretion. Further, Becn1 enhances adiponectin secretion by interacting with components of the exocyst complex via the coiled-coil domain. Together, our study demonstrates that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through binding the exocyst in adipose tissue. Kuramoto et al. demonstrate a non-degradative and non-cell-autonomous mechanism by which the autophagy protein Becn1 regulates systemic energy metabolism. Becn1 interacts with exocyst proteins in white adipose tissue to facilitate adiponectin secretion, resulting in systemic insulin sensitization via the adiponectin receptor-AMPK signaling pathway in non-adipose tissues.
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Beclin 2在自噬中功能，G蛋白偶联受体的降解和代谢。
影响因子：
64.5
作者：
He C;Wei Y;Sun K;Li B;Dong X;Zou Z;Liu Y;Kinch LN;Khan S;Sinha S;Xavier RJ;Grishin NV;Xiao G;Eskelinen EL;Scherer PE;Whistler JL;Levine B
通讯作者：
Levine B
影响因子：
4.1
作者：
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通讯作者：
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DOI：
10.1152/ajpendo.00307.2010
发表时间：
2011-02-01
影响因子：
5.1
作者：
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Abumrad, Naji N.
影响因子：
29
作者：
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通讯作者：
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影响因子：
7.7
作者：
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通讯作者：
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