Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice.
Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice.
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DOI：
10.1038/s41467-021-24914-y
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发表时间：
2021-08-06
影响因子：
16.6
通讯作者：
Seeley RJ
中科院分区：
文献类型：
--
作者：
Bozadjieva-Kramer N;Shin JH;Shao Y;Gutierrez-Aguilar R;Li Z;Heppner KM;Chiang S;Vargo SG;Granger K;Sandoval DA;MacDougald OA;Seeley RJ
减肥手术，如垂直袖胃切除术（VSG）是侵入性的，但提供最有效的改善肥胖和2型糖尿病。我们假设肠激素成纤维细胞生长因子15/19在VSG和ESTA后增加的潜在作用可以改善能量稳态和葡萄糖处理。我们产生了维持高脂肪饮食的垂体特异性FGF 15敲除（FGF 15 INT-KO）小鼠。FGF 15 INT-KO小鼠在VSG后由于增加的瘦组织损失而损失更多的重量。FGF 15 INT-KO小鼠在VSG后也丢失了更多的骨密度和骨髓脂肪组织。VSG改善葡萄糖耐量的作用在FGF 15 INT-KO中也不存在。VSG导致血浆胆汁酸水平增加，但在VSG-FGF 15 INT-KO小鼠中显著更高。这些数据表明，肠FGF 15在VSG后通过限制循环胆汁酸的增加而潜在地保护生物体免受VSG的有害作用的重要作用。介导减肥手术（如垂直袖状胃切除术（VSG））效果的机制尚未完全了解。在这里，作者表明，肠道FGF 15是必要的，以改善葡萄糖耐量和防止肌肉和骨量损失后VSG，可能通过保护对胆汁酸毒性。
Bariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive but provide the most effective improvements in obesity and Type 2 diabetes. We hypothesized a potential role for the gut hormone Fibroblast-Growth Factor 15/19 which is increased after VSG and pharmacologically can improve energy homeostasis and glucose handling. We generated intestinal-specific FGF15 knockout (FGF15INT-KO) mice which were maintained on high-fat diet. FGF15INT-KO mice lost more weight after VSG as a result of increased lean tissue loss. FGF15INT-KO mice also lost more bone density and bone marrow adipose tissue after VSG. The effect of VSG to improve glucose tolerance was also absent in FGF15INT-KO. VSG resulted in increased plasma bile acid levels but were considerably higher in VSG-FGF15INT-KO mice. These data point to an important role after VSG for intestinal FGF15 to protect the organism from deleterious effects of VSG potentially by limiting the increase in circulating bile acids. The mechanisms that mediate the effects of weight loss surgeries such as vertical sleeve gastrectomy (VSG) are incompletely understood. Here the authors show that intestinal FGF15 is necessary to improve glucose tolerance and to prevent the loss of muscle and bone mass after VSG, potentially via protection against bile acid toxicity.
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影响因子：
2.9
作者：
Belgaumkar, Ajay P.;Vincent, Royce P.;Patel, Ameet G.
通讯作者：
Patel, Ameet G.
胆汁酸主要通过进入基底外侧G蛋白偶联的胆汁酸受体触发GLP-1。
影响因子：
4.8
作者：
Brighton CA;Rievaj J;Kuhre RE;Glass LL;Schoonjans K;Holst JJ;Gribble FM;Reimann F
通讯作者：
Reimann F
影响因子：
29
作者：
Badman, Michael K.;Pissios, Pavlos;Maratos-Flier, Eleftheria
通讯作者：
Maratos-Flier, Eleftheria
影响因子：
4.8
作者：
Baker, DM;Wang, SL;Davis, RA
通讯作者：
Davis, RA
影响因子：
--
作者：
Choksi, Palak;Rothberg, Amy;Peterson, Mark
通讯作者：
Peterson, Mark