Bazuine Merlijn, Stenkula Karin G, Cam Maggie, Arroyo Mathilde, Cushman Samuel W
Experimental Diabetes, Metabolism & Nutrition Section, Diabetes Branch, NIDDK, NIH, Building 10-CRC, Room 5W-5816, 10 Center Drive, Bethesda, MD 20892, USA, Tel.: +1 301 496 7354, ,
Clin Lipidol. 2009 Apr 1;4(2):231-243. doi: 10.2217/clp.09.2.
Adipocytes provide an organism with fuel in times of caloric deficit, and are an important type of endocrine cell in the maintenance of metabolic homeostasis. In addition, as a lipid-sink, adipocytes serve an equally important role in the protection of organs from the damaging effects of ectopic lipid deposition. For the organism, it is of vital importance to maintain adipocyte viability, yet the fat depot is a demanding extracellular environment with high levels of interstitial free fatty acids and associated lipotoxic effects. These surroundings are less than beneficial for the overall health of any resident cell, adipocyte and preadipocyte alike. In this review, we discuss the process of adipogenesis and the potential involvement of the p53 tumor-suppressor protein in alleviating some of the cellular stress experienced by these cells. In particular, we discuss p53-mediated mechanisms that prevent damage caused by reactive oxygen species and the effects of lipotoxicity. We also suggest the potential for two p53 target genes, START domain-containing protein 4 (StARD4) and oxysterol-binding protein (OSBP), with the concomitant synthesis of the signaling molecule oxysterol, to participate in adipogenesis.
在热量不足时，脂肪细胞为机体提供能量，并且在维持代谢稳态方面是一种重要的内分泌细胞类型。此外，作为脂质库，脂肪细胞在保护器官免受异位脂质沉积的损害作用方面发挥着同样重要的作用。对机体而言，维持脂肪细胞的活力至关重要，然而脂肪组织是一个具有高浓度间质游离脂肪酸及相关脂毒性作用的苛刻的细胞外环境。这些环境对任何驻留细胞，无论是脂肪细胞还是前脂肪细胞的整体健康都没有益处。在本综述中，我们讨论脂肪生成过程以及p53肿瘤抑制蛋白在减轻这些细胞所经历的一些细胞应激方面的潜在作用。特别是，我们讨论了p53介导的防止活性氧引起的损伤的机制以及脂毒性的影响。我们还提出了两个p53靶基因，即含START结构域蛋白4（StARD4）和氧甾醇结合蛋白（OSBP），以及信号分子氧甾醇的伴随合成参与脂肪生成的可能性。
