Reducing insulin via conditional partial gene ablation in adults reverses diet-induced weight gain.
Reducing insulin via conditional partial gene ablation in adults reverses diet-induced weight gain.
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DOI：
10.1096/fj.201700518r
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发表时间：
2018-03
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影响因子：
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通讯作者：
Johnson JD
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文献类型：
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作者：
Page MM;Skovsø S;Cen H;Chiu AP;Dionne DA;Hutchinson DF;Lim GE;Szabat M;Flibotte S;Sinha S;Nislow C;Rodrigues B;Johnson JD
在人类和动物模型中，过量的循环胰岛素与肥胖有关。然而，高胰岛素血症在成人肥胖症中的生理因果关系受到质疑，因为缺乏明确的证据表明，体重减轻可以通过急性逆转饮食诱导的高胰岛素血症来诱导。在此，我们描述了在小鼠模型中诱导的部分胰岛素基因缺失的后果，在该模型中，动物已经通过食用高脂肪饮食而变得肥胖。胰岛素产生/分泌的适度减少足以在5周内引起显著的体重减轻，对内脏脂肪组织具有特定影响。该结果与性腺脂肪组织中脂肪代谢障碍基因聚合酶I和转录物释放因子（Ptrf; Cavin）的蛋白质丰度的减少有关。RNAseq分析显示，胰岛素减少和体重减轻也与先天免疫力降低的特征相关。这项研究表明，循环胰岛素的变化太细微，不会对葡萄糖稳态产生不利影响，但仍然可以控制肥胖。页，M。M.，斯科夫索，南，岑，H.，Chiu，A. P.，Dionne，D.一、哈钦森，D. F.、林湾，澳-地E、Szabat，M.，Flibotte，S.，辛哈，S.，尼斯洛角，Rodrigues，B.，约翰逊，J.D.在成人中通过条件性部分基因切除减少胰岛素可逆转饮食诱导的体重增加。
Excess circulating insulin is associated with obesity in humans and in animal models. However, the physiologic causality of hyperinsulinemia in adult obesity has rightfully been questioned because of the absence of clear evidence that weight loss can be induced by acutely reversing diet-induced hyperinsulinemia. Herein, we describe the consequences of inducible, partial insulin gene deletion in a mouse model in which animals have already been made obese by consuming a high-fat diet. A modest reduction in insulin production/secretion was sufficient to cause significant weight loss within 5 wk, with a specific effect on visceral adipose tissue. This result was associated with a reduction in the protein abundance of the lipodystrophy gene polymerase I and transcript release factor (Ptrf; Cavin) in gonadal adipose tissue. RNAseq analysis showed that reduced insulin and weight loss also associated with a signature of reduced innate immunity. This study demonstrates that changes in circulating insulin that are too fine to adversely affect glucose homeostasis nonetheless exert control over adiposity.—Page, M. M., Skovsø, S., Cen, H., Chiu, A. P., Dionne, D. A., Hutchinson, D. F., Lim, G. E., Szabat, M., Flibotte, S., Sinha, S., Nislow, C., Rodrigues, B., Johnson, J. D. Reducing insulin via conditional partial gene ablation in adults reverses diet-induced weight gain.