School of Basic Sciences, Indian Institute of Technology Mandi, Mandi 175001, H.P, India.
Eur J Cell Biol. 2020 Nov;99(8):151128. doi: 10.1016/j.ejcb.2020.151128. Epub 2020 Nov 2.
ChREBP is the master regulator of carbohydrate dependent glycolytic and lipogenic flux within metabolic tissues. It plays a vital role in hyper-calorific milieu by activating glycolysis, lipogenesis along with pentose phosphate shunt and glycogen synthesis, fostering immediate reduction in the systemic glycemic levels. Liver being the primary organ to sense disproportionate dietary intake and linked physiological stress, stimulates ChREBP to perform the aforementioned processes. Activated ChREBP also inhibits lipolysis and encourages proper disposal of excessive triglycerides into adipocytes from the liver ablating hepatic intracellular lipid trafficking. Chronic overeating or onset of positive energy balance, hyper-activates ChREBP and signals development, intensification of hepato-metabolic disorders, and allied discrepancies in the whole-body metabolic functioning. ChREBP thus gets negatively connotated as the primary regulator of hepatic disorders, owing to its inherent features as the primary glycemic sensor and the only transcription factor that can transduce glucose-dependent glycolytic and lipogenic signals. Through this review, we - try to recapitulate and emphasize on the sanative events coordinated by ChREBP in several pathophysiological states. In totality, we aim to uncouple the disease-causing aspects of ChREBP from its positive attributes evoked during a metabolic crisis, in hepato-metabolic diseases.
ChREBP 是代谢组织中碳水化合物依赖性糖酵解和脂肪生成通量的主要调节因子。它在高热环境中通过激活糖酵解、脂肪生成以及戊糖磷酸途径和糖原合成发挥着至关重要的作用，有助于立即降低全身血糖水平。肝脏是感知饮食摄入不成比例和相关生理压力的主要器官，它会刺激 ChREBP 来执行上述过程。激活的 ChREBP 还会抑制脂肪分解，并鼓励肝脏将过多的甘油三酯适当处理为脂肪细胞，从而消除肝内脂质转运。长期暴饮暴食或出现正能 量平衡，会过度激活 ChREBP，并发出信号，导致肝代谢紊乱的发展和加剧，以及全身代谢功能的相关差异。因此，ChREBP 被负面地归因于肝障碍的主要调节因子，这归因于其作为主要血糖传感器和唯一可以转导葡萄糖依赖性糖酵解和脂肪生成信号的转录因子的固有特征。通过这篇综述，我们试图概括和强调 ChREBP 在几种病理生理状态下协调的治疗事件。总的来说，我们旨在将 ChREBP 在肝代谢疾病中的致病方面与其在代谢危机期间引发的积极属性区分开来。
