Mor Vijay, Unnikrishnan M K
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Karnataka, India.
Endocr Metab Immune Disord Drug Targets. 2011 Sep 1;11(3):206-16. doi: 10.2174/187153011796429844.
Lifestyle changes such as physical inactivity combined with calorie-rich, low-fibre diets have triggered an explosive surge in metabolic syndrome, outlined as a cluster of heart attack risk factors such as insulin resistance, raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. By acting as a master-switch of energy homeostasis and associated pathophysiological phenomena, 5'-adenosine monophosphate-activated protein kinase (AMPK) appears to orchestrate the adaptive physiology of energy deficit, suggesting that the sedentary modern human could be suffering from chronic suboptimal AMPK activation. Addressing individual targets with potent ligands with high specificity may be inappropriate (it has not yielded any molecule superior to the sixty year old metformin) because this strategy cannot address a cluster of interrelated pathologies. However, spices, dietary supplements and nutraceuticals attenuate the multiple symptoms of metabolic syndrome in a collective and perhaps more holistic fashion with fewer adverse events. Natural selection could have favoured races that developed a taste for spices and dietary supplements, most of which are not only antioxidants but also activators of AMPK. The review will outline the various biochemical mechanisms and pathophysiological consequences of AMPK activation involving the cluster of symptoms that embrace metabolic syndrome and beyond. Recent advances that integrate energy homeostasis with a number of overarching metabolic pathways and physiological phenomena, including inflammatory conditions, cell growth and development, malignancy, life span, and even extending into environmental millieu, as in obesity mediated by gut microflora and others will also be outlined.
诸如缺乏身体活动，再加上富含热量、低纤维的饮食等生活方式的改变，引发了代谢综合征的急剧增加。代谢综合征被概括为一系列心脏病发作风险因素，如胰岛素抵抗、空腹血糖升高、腹部肥胖、高胆固醇和高血压。作为能量稳态及相关病理生理现象的主开关，5'-腺苷单磷酸激活蛋白激酶（AMPK）似乎在协调能量不足的适应性生理过程，这表明久坐不动的现代人可能正遭受慢性的AMPK激活不足。用具有高特异性的强效配体来针对个别靶点可能并不合适（尚未产生任何优于已有60年历史的二甲双胍的分子），因为这种策略无法解决一系列相互关联的病理问题。然而，香料、膳食补充剂和营养保健品可能以一种更综合、或许更全面的方式减轻代谢综合征的多种症状，且不良事件较少。自然选择可能青睐那些对香料和膳食补充剂产生喜好的人群，其中大多数不仅是抗氧化剂，还是AMPK的激活剂。本综述将概述AMPK激活涉及代谢综合征及其他相关症状群的各种生化机制和病理生理后果。还将概述将能量稳态与一些总体代谢途径和生理现象（包括炎症状态、细胞生长与发育、恶性肿瘤、寿命，甚至延伸到环境因素，如肠道微生物群介导的肥胖等）相结合的最新进展。
