Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity.
Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity.
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Insig1/SREBP1/SCD1 设定点的适应性变化有助于脂肪组织应对因肥胖而增加的储存需求。
DOI：
10.2337/db12-1748
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发表时间：
2013-11
期刊：
影响因子：
7.7
通讯作者：
Vidal-Puig A
中科院分区：
文献类型：
--
作者：
Carobbio S;Hagen RM;Lelliott CJ;Slawik M;Medina-Gomez G;Tan CY;Sicard A;Atherton HJ;Barbarroja N;Bjursell M;Bohlooly-Y M;Virtue S;Tuthill A;Lefai E;Laville M;Wu T;Considine RV;Vidal H;Langin D;Oresic M;Tinahones FJ;Fernandez-Real JM;Griffin JL;Sethi JK;López M;Vidal-Puig A
肥胖的流行对人类脂肪组织（WAT）的储存能力提出了前所未有的挑战，而这种储存能力可能受益于维持脂肪细胞功能的适应性机制。在这里，我们证明了Insig1/SREBP1调节反馈设定点控制的变化代表了在肥胖和胰岛素抵抗状态下保持WAT脂质稳态的适应性反应。在我们的实验中，我们发现肥胖相关胰岛素抵抗小鼠和病态肥胖人群以及脂肪细胞胰岛素抵抗体外模型的WAT中Insig1 mRNA表达降低。Insig1下调是适应性反应的一部分，促进SREBP1成熟的维持，促进脂肪生成和适当水平的脂肪酸不饱和，部分补偿与胰岛素抵抗相关的抗脂作用。我们首次在WAT中描述了这种适应性机制的存在，该机制涉及Insig1/SREBP1，并在肥胖诱导的胰岛素抵抗条件下保持脂质不饱和程度。尽管存在持续的代谢应激，这些适应性机制通过优先调节SCD1来维持脂质去饱和，并促进WAT中的脂肪储存。
The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.
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影响因子：
7.7
作者：
Biddinger, SB;Almind, K;Kahn, CR
通讯作者：
Kahn, CR
影响因子：
7.7
作者：
Lagathu, Claire;Christodoulides, Constantinos;Virtue, Sam;Cawthorn, William P.;Franzin, Chiara;Kimber, Wendy A.;Nora, Edoardo Dalla;Campbell, Mark;Medina-Gomez, Gema;Cheyette, Benjamin N. R.;Vidal-Puig, Antonio J.;Sethi, Jaswinder K.
通讯作者：
Sethi, Jaswinder K.
影响因子：
2.2
作者：
Ali, A. T.;Ferris, W. F.;Crowther, N. J.
通讯作者：
Crowther, N. J.
影响因子：
4.8
作者：
Le Lay, S;Lefrère, I;Krief, S
通讯作者：
Krief, S
DOI：
10.1073/pnas.1133426100
发表时间：
2003-08-05
影响因子：
11.1
作者：
Li, JP;Takaishi, K;Unger, RH
通讯作者：
Unger, RH