Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates.
Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates.
复制标题
米格列醇通过刺激棕色脂肪组织和能量消耗来防止饮食引起的肥胖，而与防止碳水化合物的消化无关。
作者：
Tsutomu Sasaki;M. Shimpuku;T. Kitazumi;Haruna Hiraga;Y. Nakagawa;H. Shibata;Y. Okamatsu;Osamu Kikuchi;Hye;Yuki Fujita;Jun Maruyama;V. Susanti;Hiromi Yokota;Masaki Kobayashi;M. Saito;T. Kitamura
米格列醇是一种α-葡萄糖苷酶抑制剂，可改善餐后高血糖，是同类药物中唯一进入血液的药物。有趣的是，米格列醇比其他α-葡萄糖苷酶抑制剂更有效地降低患者体重，但确切的机制尚未得到解决。因此，我们分析了米格列醇在小鼠和HB 2棕色脂肪细胞系中的抗肥胖作用。米格列醇通过刺激能量消耗而不影响小鼠的摄食量来预防饮食诱导的肥胖。长期米格列醇治疗剂量依赖性地预防饮食诱导的肥胖，并诱导棕色脂肪组织中的线粒体基因表达。抗肥胖作用不依赖于阻止胃肠道中的碳水化合物消化。米格列醇可有效刺激喂食高脂肪高单碳水化合物饲料的小鼠的能量消耗，腹腔注射米格列醇足以刺激小鼠的能量消耗。阿卡波糖是一种不可吸收的α葡萄糖苷酶抑制剂，也可以预防饮食引起的肥胖，但通过不同的机制：它不会刺激能量消耗，但会引起消化不良，导致能量吸收减少。米格列醇促进体外棕色脂肪细胞中的肾上腺素能信号传导。这些数据表明，循环中的米格列醇刺激棕色脂肪组织并增加能量消耗，从而预防饮食诱导的肥胖。进一步优化米格列醇对棕色脂肪组织的作用可能会导致一种新型的抗肥胖药物。
Miglitol is an alpha-glucosidase inhibitor that improves post-prandial hyperglycemia, and it is the only drug in its class that enters the bloodstream. Anecdotally, miglitol lowers patient body weight more effectively than other alpha-glucosidase inhibitors, but the precise mechanism has not been addressed. Therefore, we analyzed the anti-obesity effects of miglitol in mice and in the HB2 brown adipocyte cell line. Miglitol prevented diet-induced obesity by stimulating energy expenditure without affecting food intake in mice. Long-term miglitol treatment dose-dependently prevented diet-induced obesity and induced mitochondrial gene expression in brown adipose tissue. The anti-obesity effect was independent of preventing carbohydrate digestion in the gastrointestinal tract. Miglitol effectively stimulated energy expenditure in mice fed a high-fat high-monocarbohydrate diet, and intraperitoneal injection of miglitol was sufficient to stimulate energy expenditure in mice. Acarbose, which is a non-absorbable alpha glucosidase inhibitor, also prevented diet-induced obesity, but through a different mechanism: it did not stimulate energy expenditure, but caused indigestion, leading to less energy absorption. Miglitol promoted adrenergic signaling in brown adipocytes in vitro. These data indicate that circulating miglitol stimulates brown adipose tissue and increases energy expenditure, thereby preventing diet-induced obesity. Further optimizing miglitol's effect on brown adipose tissue could lead to a novel anti-obesity drug.
登录
查看更多内容
影响因子：
29
作者：
Seale, Patrick;Kajimura, Shingo;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.1016/j.bbapap.2003.11.029
发表时间：
2004-03-11
影响因子：
3.2
作者：
Taylor, SS;Yang, J;Anand, G
通讯作者：
Anand, G
饮食和寒冷暴露对大鼠棕色脂肪组织中去甲肾上腺素周转的影响。
DOI：
10.1172/jci110541
发表时间：
1982
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Young,JB;Saville,E;Rothwell,NJ;Stock,MJ;Landsberg,L
通讯作者：
Landsberg,L
DOI：
10.1056/nejmoa0810780
发表时间：
2009-04-09
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cypess AM;Lehman S;Williams G;Tal I;Rodman D;Goldfine AB;Kuo FC;Palmer EL;Tseng YH;Doria A;Kolodny GM;Kahn CR
通讯作者：
Kahn CR