The Molecular and Metabolic Influence of Long Term Agmatine Consumption*
The Molecular and Metabolic Influence of Long Term Agmatine Consumption*
复制标题
DOI：
10.1074/jbc.m113.544726
复制
发表时间：
2014-04-04
影响因子：
4.8
通讯作者：
Yudkoff, Marc
中科院分区：
文献类型：
--
作者：
Nissim, Itzhak;Horyn, Oksana;Yudkoff, Marc
背景：关于胍丁胺摄入对分子和代谢的影响知之甚少。结果：我们研究了长期胍丁胺治疗对大鼠全身代谢谱和基因表达的影响。胍丁胺升高[cAMP]并引发基因表达和代谢组学谱的广泛变化。结论：胍丁胺对代谢的影响可能是通过cAMP PKA介导的。意义：胍丁胺（agmatine，AGM）是精氨酸脱羧的产物，对多种生理和代谢功能有影响。然而，其作用机制、对全身基因表达和代谢途径的影响以及长期服用年度股东大会的潜在益处和风险仍然是个谜。在这里，我们仔细研究了AGM对全身代谢谱和基因表达的影响，并评估了AGM作用的合理机制。在喂食高脂肪饮食或标准食物的大鼠中进行研究。将AGM添加到饮用水中4或8周。我们使用C-13或N-15示踪剂来评估代谢反应和通量，并使用真实的时间定量PCR来确定基因表达。结果表明，AGM可提高组织中cAMP的合成和水平。随后，AGM对基因表达和代谢谱产生了广泛的影响，包括（a）过氧化物酶体增殖物激活受体及其共激活因子PGC 1的激活，以及（B）过氧化物酶体增殖物激活受体和调控产热、产酸和肉毒碱生物合成和转运的基因的表达增加。基因表达的变化，加上改善组织和全身水平的肉毒碱和短链酰基肉毒碱，增加氧化，但减少不完全脂肪酸氧化，减少脂肪，但增加蛋白质质量，并增加肝尿素生成和代谢异生，但减少糖酵解。这些代谢变化伴随着体重增加减少以及与高脂饮食诱导的肥胖相关的激素和代谢紊乱的减少。研究结果表明，AGM提高了cAMP的合成和水平，从而模拟了热量限制对代谢重编程的影响。
Background: Little is known about the molecular and metabolic impact of agmatine consumption. Results: We scrutinized the impact of long term agmatine treatment on whole body metabolic profiling and gene expression in rats. Agmatine elevated [cAMP] and triggered widespread changes in gene expression and metabolomic profiling. Conclusion: Agmatine influences on metabolism may be mediated via cAMP-PKA. Significance: Agmatine may curtail the metabolic and hormonal derangements associated with obesity.Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used C-13 or N-15 tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor- and its coactivator, PGC1, and (b) increased expression of peroxisomal proliferator-activated receptor- and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased -oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming.