营养应激、线粒体功能障碍和胰岛素抵抗

过量的营养流入细胞能量系统会导致涉及胰岛素抵抗的疾病（例如2型糖尿病）出现细胞代谢应激，称为营养应激，并导致细胞生物能量失衡，从而导致胰岛素抵抗和疾病。在营养应激下，热休克反应系统会因代谢异常而受到损害，从而扰乱能量稳态。热休克蛋白（HSP）是应激期间细胞内稳态的主要保护者。热休克反应（HSR）损伤会导致多种代谢途径加重慢性高血糖和胰岛素抵抗，凸显了其在疾病发病机制中的核心作用。本文讨论了营养应激相关分子事件在引起胰岛素抵抗中的作用，以及热休克蛋白在涉及胰岛素抵抗的分子网络的一些关键检查点中所发挥的作用的性质。充足的证据表明，热休克机制调节线粒体功能和能量代谢的关键途径，并且细胞能量状态对其影响很大。因此，热休克蛋白的减弱会导致其重要的细胞保护功能丧失，从而在系统中传播营养应激。进一步研究热休克蛋白在代谢稳态中的机制作用将有助于加深我们对生活方式疾病、其发病和并发症的理解。这些诱导蛋白可能对于减少生活方式风险因素和疾病管理至关重要。

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Excess nutrient flux into the cellular energy system results in a scenario of cellular metabolic stress in diseases involving insulin resistance, such as type 2 diabetes, referred to as nutri-stress and results in cellular bioenergetic imbalance, which leads to insulin resistance and disease. Under nutri-stress, the heat shock response system is compromised due to metabolic abnormalities that disturb energy homeostasis. Heat shock proteins (HSPs) are the chief protectors of intracellular homeostasis during stress. Heat shock response (HSR) impairment contributes to several metabolic pathways that aggravate chronic hyperglycaemia and insulin resistance, highlighting a central role in disease pathogenesis. This article discusses the role of nutri-stress-related molecular events in causing insulin resistance and the nature of the roles played by heat shock proteins in some of the crucial checkpoints of the molecular networks involved in insulin resistance. Ample evidence suggests that the heat shock machinery regulates critical pathways in mitochondrial function and energy metabolism and that cellular energy status highly influences it. Weakening of HSPs, therefore, leads to loss of their vital cytoprotective functions, propagating nutri-stress in the system. Further research into the mechanistic roles of HSPs in metabolic homeostasis will help widen our understanding of lifestyle diseases, their onset, and complications. These inducible proteins may be crucial to attenuating lifestyle risk factors and disease management.