Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats.
Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats.
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DOI：
10.1371/journal.pone.0071944
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ceddia RB
中科院分区：
文献类型：
--
作者：
Vitzel KF;Bikopoulos G;Hung S;Curi R;Ceddia RB
本研究测试了长期全身给予5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）是否可以减轻胰岛素缺乏大鼠的摄食过多，减少瘦体重和脂肪量损失，并改善全身能量稳态。首先通过链脲佐菌素（STZ）给药使雄性Wistar大鼠患糖尿病，然后连续7天腹腔注射AICAR。在AICAR治疗期结束时，对食物和水的摄入量、步行活动和能量消耗进行评估。收集血液用于循环瘦素测量，并提取下丘脑用于测定细胞因子信号传导抑制因子3（SOCS 3）含量，以及AMP激酶（AMPK）、乙酰辅酶A羧化酶（ACC）和信号转导和转录激活因子3（STAT 3）的含量和磷酸化。将大鼠彻底解剖以测定肥胖和瘦体重（LBM）。在非糖尿病大鼠中，尽管减少了肥胖，AICAR增加了（1.7倍）循环瘦素，并减少了下丘脑SOCS 3含量和食物摄入量分别为67%和25%。AICAR的抗糖尿病作用在糖尿病大鼠中丧失，即使这些动物的下丘脑AMPK和ACC磷酸化显著降低。重要的是，在用AICAR治疗胰岛素缺乏大鼠后，下丘脑SOCS 3和STAT 3水平分别保持升高和降低。糖尿病大鼠嗜睡，脂肪和LBM明显减少。AICAR治疗增加了步行活动和全身能量消耗，同时也减少了糖尿病引起的脂肪和LBM损失。总之，AICAR没有逆转暴食症，但它促进了对骨骼肌和脂肪的抗分解代谢作用，增强了自发的体力活动，并提高了大鼠科普糖尿病诱导的葡萄糖代谢和全身能量稳态功能失调的能力。
This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats. Male Wistar rats were first rendered diabetic through streptozotocin (STZ) administration and then intraperitoneally injected with AICAR for 7 consecutive days. Food and water intake, ambulatory activity, and energy expenditure were assessed at the end of the AICAR-treatment period. Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3). Rats were thoroughly dissected for adiposity and lean body mass (LBM) determinations. In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively. The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals. Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR. Diabetic rats were lethargic and displayed marked losses of fat and LBM. AICAR treatment increased ambulatory activity and whole-body energy expenditure while also attenuating diabetes-induced fat and LBM losses. In conclusion, AICAR did not reverse hyperphagia, but it promoted anti-catabolic effects on skeletal muscle and fat, enhanced spontaneous physical activity, and improved the ability of rats to cope with the diabetes-induced dysfunctional alterations in glucose metabolism and whole-body energy homeostasis.
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影响因子：
7.7
作者：
Pold, R;Jensen, LS;Lund, S
通讯作者：
Lund, S
影响因子：
7.7
作者：
Hunter RW;Treebak JT;Wojtaszewski JF;Sakamoto K
通讯作者：
Sakamoto K
影响因子：
7.7
作者：
Buhl, ES;Jessen, N;Lund, S
通讯作者：
Lund, S
DOI：
10.1016/j.cppeds.2012.07.002
发表时间：
2012-11-01
影响因子：
1.6
作者：
Gan, Mary Joyce;Albanese-O'Neill, Anastasia;Haller, Michael J.
通讯作者：
Haller, Michael J.
影响因子：
82.9
作者：
Howard, JK;Cave, BJ;Flier, JS
通讯作者：
Flier, JS