Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver.
Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver.
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DOI：
10.2337/db11-0455
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发表时间：
2011-11
期刊：
影响因子：
7.7
通讯作者：
Wasserman DH
中科院分区：
文献类型：
--
作者：
Berglund ED;Lustig DG;Baheza RA;Hasenour CM;Lee-Young RS;Donahue EP;Lynes SE;Swift LL;Charron MJ;Damon BM;Wasserman DH
运动是治疗脂肪肝的有效干预措施。然而，运动引起的脂肪肝减少的机制尚不清楚。在这里，我们检验了运动需要肝胰高血糖素作用来减少脂肪肝的假设。 C57BL/6 小鼠被喂食高脂肪饮食 (HFD)，并使用磁共振、生化和组织学技术进行评估，以确定 20 周内脂肪肝发展的时间表。随后给胰高血糖素受体无效 (gcgr−/−) 和野生型 (gcgr+/+) 同窝小鼠喂食 HFD 以引发中度脂肪肝，然后分别进行 10 周或 6 周的跑轮或跑步机运动。运动可逆转 gcgr+/+ 小鼠中 HFD 诱导的脂肪肝进展。值得注意的是，gcgr−/− 小鼠中不存在这种变化，从而证实了运动刺激的肝胰高血糖素受体激活对于减少 HFD 诱导的脂肪肝至关重要的假设。这些发现表明，利用拮抗肝胰高血糖素作用来降低血糖的疗法可能会干扰运动能力，或许还会干扰其他积极影响脂肪肝的干预措施。
Exercise is an effective intervention to treat fatty liver. However, the mechanism(s) that underlie exercise-induced reductions in fatty liver are unclear. Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver. C57BL/6 mice were fed high-fat diet (HFD) and assessed using magnetic resonance, biochemical, and histological techniques to establish a timeline for fatty liver development over 20 weeks. Glucagon receptor null (gcgr−/−) and wild-type (gcgr+/+) littermate mice were subsequently fed HFD to provoke moderate fatty liver and then performed either 10 or 6 weeks of running wheel or treadmill exercise, respectively. Exercise reverses progression of HFD-induced fatty liver in gcgr+/+ mice. Remarkably, such changes are absent in gcgr−/− mice, thus confirming the hypothesis that exercise-stimulated hepatic glucagon receptor activation is critical to reduce HFD-induced fatty liver. These findings suggest that therapies that use antagonism of hepatic glucagon action to reduce blood glucose may interfere with the ability of exercise and perhaps other interventions to positively affect fatty liver.
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影响因子：
29
作者：
Longuet, Christine;Sinclair, Elaine M.;Drucker, Daniel J.
通讯作者：
Drucker, Daniel J.
影响因子：
16.2
作者：
Larson-Meyer, D. Enette;Heilbronn, Leonie K.;Ravussin, Eric
通讯作者：
Ravussin, Eric
DOI：
10.1152/ajpendo.00309.2007
发表时间：
2008-09-01
影响因子：
5.1
作者：
Bradley, Richard L.;Jeon, Justin Y.;Maratos-Flier, Eleftheria
通讯作者：
Maratos-Flier, Eleftheria
DOI：
10.1111/j.1440-1746.2005.04233.x
发表时间：
2006-01-01
影响因子：
4.1
作者：
Baba, CS;Alexander, G;Choudhuri, G
通讯作者：
Choudhuri, G
影响因子：
29
作者：
Badman, Michael K.;Pissios, Pavlos;Maratos-Flier, Eleftheria
通讯作者：
Maratos-Flier, Eleftheria