酮体代谢的调节及过氧化物酶体增殖物激活受体α的作用

Grabacka Maja, Pierzchalska Malgorzata, Dean Matthew, Reiss Krzysztof

Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture, ul. Balicka 122, 30-149 Kraków, Poland.

Neurological Cancer Research, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, 1700 Tulane Ave, New Orleans, LA 70112, USA.

Int J Mol Sci. 2016 Dec 13;17(12):2093. doi: 10.3390/ijms17122093.

Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.

生酮作用和酮体分解是禁食反应过程中激活的核心代谢过程。生酮作用在多个阶段受到调控，核受体过氧化物酶体增殖物激活受体α（PPARα）是参与这一调控的关键转录因子之一。PPARα是代谢网络中的一个重要元件，它参与由主要营养传感器驱动的信号传导，如AMP激活的蛋白激酶（AMPK）、PPARγ共激活因子1α（PGC-1α）和哺乳动物雷帕霉素靶蛋白（mTOR），并诱导激素介质，如成纤维细胞生长因子21（FGF21）。这项工作描述了正常细胞和恶性细胞中生酮作用和酮体分解的调控，并简要总结了酮体在各种神经病理状况下的积极作用。