Vertical sleeve gastrectomy normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice.
Vertical sleeve gastrectomy normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice.
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DOI：
10.3389/fendo.2022.1020576
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发表时间：
2022
影响因子：
5.2
通讯作者：
Rutter, Guy A.
中科院分区：
文献类型：
--
作者：
Akalestou, Elina;Lopez-Noriega, Livia;Christakis, Ioannis;Hu, Ming;Miras, Alexander D.;Leclerc, Isabelle;Rutter, Guy A.
肾上腺皮质产生的糖皮质激素对于维持代谢平衡是必不可少的。糖皮质激素的活化由11β-羟基类固醇脱氢酶1（11β-HSD 1）催化。过量的糖皮质激素与胰岛素抵抗和高血糖症有关。少数研究已证实减肥手术对糖皮质激素代谢的影响，减肥手术是一组已知可改善胰岛素敏感性和分泌的胃肠道手术，被认为是体重减轻的结果。在这项研究中，我们假设减肥手术后糖皮质激素作用的减少有助于广泛观察到的治疗的血糖正常作用。术后10周进行葡萄糖和胰岛素耐量试验，并测定循环皮质酮。从进食的小鼠中收获肝脏和脂肪组织，并分别通过定量RT-PCR或Western（免疫）印迹法测量11β-HSD 1水平。使用CRISPR/Cas9基因组编辑产生11β-HSD 1缺失小鼠（Hsd 11b 1-/-）。野生型和同窝Hsd 11b 1-/-小鼠接受垂直袖状胃切除术（VSG）或假手术。 在所用条件下，在VSG处理和假手术小鼠之间未观察到体重减轻差异。然而，瘦型和肥胖型WT VSG小鼠均显示出显著改善的葡萄糖清除率和胰岛素敏感性。值得注意的是，VSG恢复了HFD小鼠的生理皮质酮产生，并减少了手术后肝脏和脂肪组织中的11β-HSD 1表达。通过CRISPR/Cas9消除11β-HSD 1/Hsd 11b 1基因模拟了VSG对体重和对1g/kg葡萄糖挑战的耐受性的影响。然而，在较高的葡萄糖负荷下，VSG的血糖正常效应上级优于Hsd 11 b1消除。在生理和病理生理（肥胖）条件下，减肥手术可改善胰岛素敏感性，减少组织水平糖皮质激素的激活，与体重减轻无关。这些研究结果指向一个生理相关的肠道糖皮质激素轴，并表明，降低糖皮质激素暴露可能代表减肥手术的健康益处的额外贡献。
Glucocorticoids produced by the adrenal cortex are essential for the maintenance of metabolic homeostasis. Glucocorticoid activation is catalysed by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). Excess glucocorticoids are associated with insulin resistance and hyperglycaemia. A small number of studies have demonstrated effects on glucocorticoid metabolism of bariatric surgery, a group of gastrointestinal procedures known to improve insulin sensitivity and secretion, which were assumed to result from weight loss. In this study, we hypothesize that a reduction in glucocorticoid action following bariatric surgery contributes to the widely observed euglycemic effects of the treatment. Glucose and insulin tolerance tests were performed at ten weeks post operatively and circulating corticosterone was measured. Liver and adipose tissues were harvested from fed mice and 11β-HSD1 levels were measured by quantitative RT-PCR or Western (immuno-) blotting, respectively. 11β-HSD1 null mice (Hsd11b1 -/-) were generated using CRISPR/Cas9 genome editing. Wild type and littermate Hsd11b1 -/- mice underwent Vertical Sleeve Gastrectomy (VSG) or sham surgery. Under the conditions used, no differences in weight loss were observed between VSG treated and sham operated mice. However, both lean and obese WT VSG mice displayed significantly improved glucose clearance and insulin sensitivity. Remarkably, VSG restored physiological corticosterone production in HFD mice and reduced 11β-HSD1 expression in liver and adipose tissue post-surgery. Elimination of the 11β-HSD1/Hsd11b1 gene by CRISPR/Cas9 mimicked the effects of VSG on body weight and tolerance to 1g/kg glucose challenge. However, at higher glucose loads, the euglycemic effect of VSG was superior to Hsd11b1 elimination. Bariatric surgery improves insulin sensitivity and reduces glucocorticoid activation at the tissular level, under physiological and pathophysiological (obesity) conditions, irrespective of weight loss. These findings point towards a physiologically relevant gut-glucocorticoid axis, and suggest that lowered glucocorticoid exposure may represent an additional contribution to the health benefits of bariatric surgery.
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影响因子：
7.7
作者：
Argaud, D;Zhang, Q;Lange, AJ
通讯作者：
Lange, AJ
影响因子：
16.6
作者：
Akalestou E;Suba K;Lopez-Noriega L;Georgiadou E;Chabosseau P;Gallie A;Wretlind A;Legido-Quigley C;Leclerc I;Salem V;Rutter GA
通讯作者：
Rutter GA
影响因子：
8
作者：
Iynedjian, P. B.
通讯作者：
Iynedjian, P. B.
影响因子：
8.2
作者：
Cummings DE;Arterburn DE;Westbrook EO;Kuzma JN;Stewart SD;Chan CP;Bock SN;Landers JT;Kratz M;Foster-Schubert KE;Flum DR
通讯作者：
Flum DR
DOI：
10.1152/ajpendo.00469.2013
发表时间：
2014-02-01
影响因子：
5.1
作者：
Chambers, Adam P.;Smith, Eric P.;Sandoval, Darleen A.
通讯作者：
Sandoval, Darleen A.