PARPs and tankyrases (TNKS) represent a family of 17 proteins. PARPs and tankyrases were originally identified as DNA repair factors, nevertheless, recent advances have shed light on their role in lipid metabolism. To date, PARP1, PARP2, PARP3, tankyrases, PARP9, PARP10, PARP14 were reported to have multi-pronged connections to lipid metabolism. The activity of PARP enzymes is fine-tuned by a set of cholesterol-based compounds as oxidized cholesterol derivatives, steroid hormones or bile acids. In turn, PARPs modulate several key processes of lipid homeostasis (lipotoxicity, fatty acid and steroid biosynthesis, lipoprotein homeostasis, fatty acid oxidation, etc.). PARPs are also cofactors of lipid-responsive nuclear receptors and transcription factors through which PARPs regulate lipid metabolism and lipid homeostasis. PARP activation often represents a disruptive signal to (lipid) metabolism, and PARP-dependent changes to lipid metabolism have pathophysiological role in the development of hyperlipidemia, obesity, alcoholic and non-alcoholic fatty liver disease, type II diabetes and its complications, atherosclerosis, cardiovascular aging and skin pathologies, just to name a few. In this synopsis we will review the evidence supporting the beneficial effects of pharmacological PARP inhibitors in these diseases/pathologies and propose repurposing PARP inhibitors already available for the treatment of various malignancies.

PARPs 和 tankyrases (TNKS) 代表 17 种蛋白质的家族。PARPs 和 tankyrases 最初被确定为 DNA 修复因子，然而，最近的进展揭示了它们在脂质代谢中的作用。迄今为止，据报道 PARP1、PARP2、PARP3、tankyrases、PARP9、PARP10、PARP14 与脂质代谢具有多方面的联系。PARP 酶的活性由一组基于胆固醇的化合物（如氧化胆固醇衍生物、类固醇激素或胆汁酸）进行微调。反过来，PARPs 调节脂质稳态的几个关键过程（脂毒性、脂肪酸和类固醇生物合成、脂蛋白稳态、脂肪酸氧化等）。PARPs 也是脂质反应性核受体和转录因子的辅助因子，PARPs 通过它们调节脂质代谢和脂质稳态。PARP 激活通常代表（脂质）代谢的破坏性信号，并且 PARP 依赖性脂质代谢变化在高脂血症、肥胖、酒精性和非酒精性脂肪肝疾病、II 型糖尿病及其并发症、动脉粥样硬化、心血管老化和皮肤病变，仅举几例。在本概要中，我们将回顾支持药理学 PARP 抑制剂在这些疾病/病理学中的有益作用的证据，并建议重新利用已经可用于治疗各种恶性肿瘤的 PARP 抑制剂。II 型糖尿病及其并发症、动脉粥样硬化、心血管老化和皮肤病，仅举几例。在本概要中，我们将回顾支持药理学 PARP 抑制剂在这些疾病/病理学中的有益作用的证据，并建议重新利用已经可用于治疗各种恶性肿瘤的 PARP 抑制剂。II 型糖尿病及其并发症、动脉粥样硬化、心血管老化和皮肤病，仅举几例。在本概要中，我们将回顾支持药理学 PARP 抑制剂在这些疾病/病理学中的有益作用的证据，并建议重新利用已经可用于治疗各种恶性肿瘤的 PARP 抑制剂。