Energy status regulates levels of the RAR/RXR ligand 9-cis-retinoic acid in mammalian tissues: Glucose reduces its synthesis in β-cells.
Energy status regulates levels of the RAR/RXR ligand 9-cis-retinoic acid in mammalian tissues: Glucose reduces its synthesis in β-cells.
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DOI：
10.1016/j.jbc.2023.105255
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发表时间：
2023-10
影响因子：
4.8
通讯作者：
Napoli, Joseph L.
中科院分区：
文献类型：
--
作者：
Yoo, Hong Sik;Moss, Kristin Obrochta;Cockrum, Michael A.;Woo, Wonsik;Napoli, Joseph L.
9-顺式视黄酸（9cRA）以纳摩尔亲和力与视黄酸受体（RAR）和类视黄醇X受体（RXR）结合，而全反式视黄酸（atRA）仅以纳摩尔亲和力与RAR结合。RXR与包括RAR在内的II型核受体形成异源二聚体，以调控大量基因。尽管付出诸多努力，除了胰腺之外，9cRA尚未被确定为一种内源性类视黄醇。通过改进组织分析方法，利用液相色谱 - 串联质谱法对所分析的所有小鼠组织中的9cRA进行定量成为可能。9cRA的浓度与atRA相似或更高。禁食会使白色和棕色脂肪组织、大脑及胰腺中的9cRA增加，同时使白色脂肪组织、肝脏和胰腺中的atRA增加。9cRA支持胰腺β细胞中FoxO1的作用，并抵消导致糖毒性的葡萄糖作用；部分是通过诱导Atg7信使核糖核酸（mRNA）实现的，Atg7编码自噬所必需的关键酶。葡萄糖抑制β细胞系832/13和MIN6中9cRA的生物合成。在832/13细胞中，葡萄糖通过环磷腺苷（cAMP）和蛋白激酶B（Akt）抑制Rdh5转录（与胰岛素无关）并抑制FoxO1，从而减少9cRA的生物合成。9cRA通过使组织特异性地适应禁食状态，其作用独立于atRA。9cRA在体内广泛存在，且能自主适应能量状态，这为能量平衡调节、胰岛素和葡萄糖作用的减弱、II型核受体的调控以及类视黄醇生物学提供了新的视角。
9-cis-retinoic acid (9cRA) binds retinoic acid receptors (RAR) and retinoid X receptors (RXR) with nanomolar affinities, in contrast to all-trans-retinoic acid (atRA), which binds only RAR with nanomolar affinities. RXR heterodimerize with type II nuclear receptors, including RAR, to regulate a vast gene array. Despite much effort, 9cRA has not been identified as an endogenous retinoid, other than in pancreas. By revising tissue analysis methods, 9cRA quantification by liquid chromatography-tandem mass spectrometry becomes possible in all mouse tissues analyzed. 9cRA occurs in concentrations similar to or greater than atRA. Fasting increases 9cRA in white and brown adipose, brain and pancreas, while increasing atRA in white adipose, liver and pancreas. 9cRA supports FoxO1 actions in pancreas β-cells and counteracts glucose actions that lead to glucotoxicity; in part by inducing Atg7 mRNA, which encodes the key enzyme essential for autophagy. Glucose suppresses 9cRA biosynthesis in the β-cell lines 832/13 and MIN6. Glucose reduces 9cRA biosynthesis in 832/13 cells by inhibiting Rdh5 transcription, unconnected to insulin, through cAMP and Akt, and inhibiting FoxO1. Through adapting tissue specifically to fasting, 9cRA would act independent of atRA. Widespread occurrence of 9cRA in vivo, and its self-sufficient adaptation to energy status, provides new perspectives into regulation of energy balance, attenuation of insulin and glucose actions, regulation of type II nuclear receptors, and retinoid biology.
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影响因子：
4.6
作者：
Napoli, Joseph L.
通讯作者：
Napoli, Joseph L.
影响因子：
5.8
作者：
Yoo HS;Rodriguez A;You D;Lee RA;Cockrum MA;Grimes JA;Wang JC;Kang S;Napoli JL
通讯作者：
Napoli JL
DOI：
10.1111/febs.16221
发表时间：
2022-12
期刊：
The FEBS journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
HEYMAN, RA;MANGELSDORF, DJ;THALLER, C
通讯作者：
THALLER, C
影响因子：
2.9
作者：
Wang J;Yoo HS;Obrochta KM;Huang P;Napoli JL
通讯作者：
Napoli JL