Jokinen Riikka, Pirnes-Karhu Sini, Pietiläinen Kirsi H, Pirinen Eija
Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, Biomedicum Helsinki, University of Helsinki, Biomedicum Helsinki, Helsinki, Finland.
Molecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Redox Biol. 2017 Aug;12:246-263. doi: 10.1016/j.redox.2017.02.011. Epub 2017 Feb 27.
Obesity, a chronic state of energy overload, is characterized by adipose tissue dysfunction that is considered to be the major driver for obesity associated metabolic complications. The reasons for adipose tissue dysfunction are incompletely understood, but one potential contributing factor is adipose tissue mitochondrial dysfunction. Derangements of adipose tissue mitochondrial biogenesis and pathways associate with obesity and metabolic diseases. Mitochondria are central organelles in energy metabolism through their role in energy derivation through catabolic oxidative reactions. The mitochondrial processes are dependent on the proper NAD/NADH redox balance and NAD is essential for reactions catalyzed by the key regulators of mitochondrial metabolism, sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs). Notably, obesity is associated with disturbed adipose tissue NAD homeostasis and the balance of SIRT and PARP activities. In this review we aim to summarize existing literature on the maintenance of intracellular NAD pools and the function of SIRTs and PARPs in adipose tissue during normal and obese conditions, with the purpose of comprehending their potential role in mitochondrial derangements and obesity associated metabolic complications. Understanding the molecular mechanisms that are the root cause of the adipose tissue mitochondrial derangements is crucial for developing new effective strategies to reverse obesity associated metabolic complications.
肥胖是一种能量长期过载的慢性状态，其特征是脂肪组织功能障碍，这被认为是肥胖相关代谢并发症的主要驱动因素。脂肪组织功能障碍的原因尚未完全明确，但一个潜在的促成因素是脂肪组织线粒体功能障碍。脂肪组织线粒体生物合成和途径的紊乱与肥胖和代谢性疾病相关。线粒体是能量代谢的核心细胞器，通过分解代谢氧化反应在能量产生中发挥作用。线粒体过程依赖于适当的NAD/NADH氧化还原平衡，NAD对于线粒体代谢关键调节因子——沉默调节蛋白（SIRTs）和聚（ADP-核糖）聚合酶（PARPs）催化的反应至关重要。值得注意的是，肥胖与脂肪组织NAD稳态紊乱以及SIRT和PARP活性平衡有关。在本综述中，我们旨在总结现有文献中关于正常和肥胖状态下细胞内NAD池的维持以及SIRTs和PARPs在脂肪组织中的功能，目的是了解它们在线粒体紊乱和肥胖相关代谢并发症中的潜在作用。了解脂肪组织线粒体紊乱根本原因的分子机制对于开发逆转肥胖相关代谢并发症的新有效策略至关重要。
