Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss.
Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss.
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溶酶体介导间歇性禁食对心脏代谢疾病的益处：清洁工竟是幕后老板 。
DOI：
10.1002/cphy.c180005
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发表时间：
2018-09-14
影响因子：
5.8
通讯作者：
Diwan A
中科院分区：
文献类型：
--
作者：
Mani K;Javaheri A;Diwan A
对抗饥饿的适应性反应已经进化了数千年，以允许生物体生存，包括个体细胞器，细胞，组织和器官系统水平的变化。在过去的世纪中，由营养供应不足引起的疾病已经转向营养过剩，导致肥胖和糖尿病、动脉粥样硬化和心脏代谢疾病。这些疾病的负担激发了人们对禁食策略的兴趣，这些策略利用了对饥饿的生理反应，从而限制了代谢应激期间的组织损伤。从动物和人类研究中获得的见解表明，间歇性禁食和慢性热量限制可延长寿命，减少心脏代谢和炎症疾病的风险因素，限制心肌应激期间的组织损伤，并激活心脏保护代谢程序。急性禁食激活自噬，这是一种错综复杂的溶酶体降解过程，可隔离细胞成分进行降解，并且对禁食期间的心脏稳态至关重要。溶酶体是动态的细胞器，其作为焚化器起作用以允许自噬，以及降解通过内吞作用、巨胞饮作用和吞噬作用内化的细胞外物质。在过去的十年里，我们见证了知识的爆炸，这些知识塑造了我们对溶酶体作为细胞代谢和禁食反应的中央调节器的理解。有趣的是，溶酶体还储存营养素以在饥饿期间释放;并且作为营养素感测细胞器将mTOR的激活与营养素可用性偶联。本文综述了溶酶体如何伪装成看门人，可能是指导细胞过程的“卧底老板”，以获得间歇性禁食的有益效果，并在盛宴和饥荒期间恢复体内平衡的证据。
Adaptive responses that counter starvation have evolved over millennia to permit organismal survival, including changes at the level of individual organelles, cells, tissues, and organ systems. In the past century, a shift has occurred away from disease caused by insufficient nutrient supply towards over-nutrition, leading to obesity and diabetes, atherosclerosis, and cardiometabolic disease. The burden of these diseases has spurred interest in fasting strategies that harness physiological responses to starvation, thus limiting tissue injury during metabolic stress. Insights gained from animal and human studies suggest that intermittent fasting and chronic caloric restriction extend lifespan, decrease risk factors for cardio-metabolic and inflammatory disease, limit tissue injury during myocardial stress, and activate a cardioprotective metabolic program. Acute fasting activates autophagy, an intricately orchestrated lysosomal degradative process that sequesters cellular constituents for degradation, and is critical for cardiac homeostasis during fasting. Lysosomes are dynamic cellular organelles that function as incinerators to permit autophagy, as well as degradation of extracellular material internalized by endocytosis, macropinocytosis and phagocytosis. The last decade has witnessed an explosion of knowledge that has shaped our understanding of lysosomes as central regulators of cellular metabolism and the fasting response. Intriguingly, lysosomes also store nutrients for release during starvation; and function as a nutrient sensing organelle to couple activation of mTOR to nutrient availability. This article reviews the evidence for how the lysosome, in the guise of a janitor, may be the ‘undercover boss’ directing cellular processes for beneficial effects of intermittent fasting and restoring homeostasis during feast and famine.
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影响因子：
29
作者：
Brandhorst S;Choi IY;Wei M;Cheng CW;Sedrakyan S;Navarrete G;Dubeau L;Yap LP;Park R;Vinciguerra M;Di Biase S;Mirzaei H;Mirisola MG;Childress P;Ji L;Groshen S;Penna F;Odetti P;Perin L;Conti PS;Ikeno Y;Kennedy BK;Cohen P;Morgan TE;Dorff TB;Longo VD
通讯作者：
Longo VD
影响因子：
5.8
作者：
Amamou, T.;Normandin, E.;Riesco, E.
通讯作者：
Riesco, E.
影响因子：
56.9
作者：
Brunet, A;Sweeney, LB;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1093/gerona/glw064
发表时间：
2016-07-01
影响因子：
5.1
作者：
Apelo, Sebastian I. Arriola;Pumper, Cassidy P.;Lamming, Dudley W.
通讯作者：
Lamming, Dudley W.
热量限制：对人类心脏代谢健康的影响。
DOI：
10.1097/hcr.0b013e318295019e
发表时间：
2013-07
影响因子：
3.8
作者：
Bales CW;Kraus WE
通讯作者：
Kraus WE