Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance.
Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance.
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脂肪素对具有胰岛素抵抗的饮食诱导的肥胖小鼠中葡萄糖耐受性和底物利用的治疗作用。
DOI：
10.1016/j.molmet.2015.01.005
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发表时间：
2015-04
影响因子：
8.1
通讯作者：
Butler AA
中科院分区：
文献类型：
--
作者：
Gao S;McMillan RP;Zhu Q;Lopaschuk GD;Hulver MW;Butler AA
肽激素肾上腺素调节燃料的选择偏好骨骼肌在进食和禁食条件下。在这里，我们研究了Adropin治疗是否可以改善燃料底物代谢的失调，并改善饮食诱导的肥胖症（DIO）伴胰岛素抵抗的葡萄糖稳态方面。维持在60%kcal脂肪饮食的DIO C57 BL/6小鼠接受5次腹膜内（i. p.）注射生物活性肽adropin 34 -76（450 nmol/kg/i. p.）。治疗后，评估葡萄糖耐量和全身胰岛素敏感性，并采用间接量热法分析全身底物氧化偏好。在骨骼肌样品中进行的生化测定分析了胰岛素信号传导作用和底物氧化。Adropin治疗改善了葡萄糖耐量，增强了胰岛素作用，增强了葡萄糖利用的代谢灵活性。在肌肉中，Adropin处理增加胰岛素诱导的Akt磷酸化和细胞表面GLUT 4表达，表明胰岛素信号通路的敏化。减少不完全脂肪酸氧化和增加CoA/乙酰辅酶A的比例表明改善线粒体功能。其潜在机制似乎涉及脂肪酸利用中的两种关键酶肉毒碱棕榈酰转移酶-1B（CPT-1B）和CD 36的抑制。Adropin处理激活了丙酮酸脱氢酶（PDH），一种葡萄糖氧化的限速酶，并下调了抑制PDH的PDH激酶-4（PDK-4）。沿着这些变化，阿霉素处理下调了过氧化物酶体增殖物激活受体-γ共激活因子-1 α，其调节Cpt 1b、Cd 36和Pdk 4的表达。Adropin治疗DIO小鼠增强葡萄糖耐量，改善胰岛素抵抗，并促进在燃料选择中优先使用碳水化合物而不是脂肪。骨骼肌是介导Adropin的全身效应、使胰岛素信号传导途径敏感以及改变燃料选择偏好以有利于葡萄糖同时抑制脂肪氧化的关键器官。
The peptide hormone adropin regulates fuel selection preferences in skeletal muscle under fed and fasted conditions. Here, we investigated whether adropin treatment can ameliorate the dysregulation of fuel substrate metabolism, and improve aspects of glucose homeostasis in diet-induced obesity (DIO) with insulin resistance. DIO C57BL/6 mice maintained on a 60% kcal fat diet received five intraperitoneal (i.p.) injections of the bioactive peptide adropin34-76 (450 nmol/kg/i.p.). Following treatment, glucose tolerance and whole body insulin sensitivity were assessed and indirect calorimetry was employed to analyze whole body substrate oxidation preferences. Biochemical assays performed in skeletal muscle samples analyzed insulin signaling action and substrate oxidation. Adropin treatment improved glucose tolerance, enhanced insulin action and augmented metabolic flexibility towards glucose utilization. In muscle, adropin treatment increased insulin-induced Akt phosphorylation and cell-surface expression of GLUT4 suggesting sensitization of insulin signaling pathways. Reduced incomplete fatty acid oxidation and increased CoA/acetyl-CoA ratio suggested improved mitochondrial function. The underlying mechanisms appear to involve suppressions of carnitine palmitoyltransferase-1B (CPT-1B) and CD36, two key enzymes in fatty acid utilization. Adropin treatment activated pyruvate dehydrogenase (PDH), a rate-limiting enzyme in glucose oxidation, and downregulated PDH kinase-4 (PDK-4) that inhibits PDH. Along with these changes, adropin treatment downregulated peroxisome proliferator-activated receptor-gamma coactivator-1α that regulates expression of Cpt1b, Cd36 and Pdk4. Adropin treatment of DIO mice enhances glucose tolerance, ameliorates insulin resistance and promotes preferential use of carbohydrate over fat in fuel selection. Skeletal muscle is a key organ in mediating adropin's whole-body effects, sensitizing insulin signaling pathways and altering fuel selection preference to favor glucose while suppressing fat oxidation.
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影响因子：
3.7
作者：
Crewe C;Kinter M;Szweda LI
通讯作者：
Szweda LI
小儿阻塞性睡眠呼吸暂停中循环的adropin浓度：与内皮功能的潜在相关性。
DOI：
10.1016/j.jpeds.2013.05.040
发表时间：
2013-10
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Gozal D;Kheirandish-Gozal L;Bhattacharjee R;Molero-Ramirez H;Tan HL;Bandla HP
通讯作者：
Bandla HP
影响因子：
2.4
作者：
Celik, Ebru;Yilmaz, Ercan;Aydin, Suleyman
通讯作者：
Aydin, Suleyman
影响因子：
3.5
作者：
Ekstrand, MI;Falkenberg, M;Larsson, NG
通讯作者：
Larsson, NG
影响因子：
16
作者：
Bruning, JC;Michael, MD;Kahn, CR
通讯作者：
Kahn, CR