Bombarda-Rocha Victória, Silva Dany, Badr-Eddine Allal, Nogueira Patrícia, Gonçalves Jorge, Fresco Paula
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
UCIBIO-Applied Molecular Biosciences Unit, Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Cancers (Basel). 2023 Aug 7;15(15):4013. doi: 10.3390/cancers15154013.
Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1-5), each with specific expression patterns and metabolic activation, but all capable of regulating the activity of lipases on LD. This plurality creates a complex orchestrated mechanism that is directly related to the healthy balance between lipogenesis and lipolysis. Given the essential role of PLINs in the modulation of the lipid metabolism, these proteins can become interesting targets for the treatment of lipid-associated diseases. Since reprogrammed lipid metabolism is a recognized cancer hallmark, and obesity is a known risk factor for cancer and other comorbidities, the modulation of PLINs could either improve existing treatments or create new opportunities for the treatment of these diseases. Even though PLINs have not been, so far, directly considered for pharmacological interventions, there are many established drugs that can modulate PLINs activity. Therefore, the aim of this study is to assess the involvement of PLINs in diseases related to lipid metabolism dysregulation and whether PLINs can be viewed as potential therapeutic targets for cancer and obesity.
周脂素（PLINs）是脂滴（LD）中含量最丰富的蛋白质。这些与脂滴相关的蛋白质负责将脂滴从惰性脂质储存结构提升为功能完备的细胞器，使其从根本上融入脂质代谢过程。周脂素有五种不同类型（PLIN1 - 5），每种都有特定的表达模式和代谢激活方式，但都能够调节脂滴上脂肪酶的活性。这种多样性形成了一种复杂的协调机制，该机制与脂肪生成和脂肪分解之间的健康平衡直接相关。鉴于周脂素在调节脂质代谢中起着至关重要的作用，这些蛋白质可能成为治疗脂质相关疾病的有趣靶点。由于脂质代谢重编程是公认的癌症标志，且肥胖是癌症和其他合并症的已知风险因素，调节周脂素可能会改善现有治疗方法，或者为这些疾病的治疗创造新机会。尽管到目前为止，周脂素尚未被直接考虑用于药物干预，但有许多已有的药物可以调节周脂素的活性。因此，本研究的目的是评估周脂素在与脂质代谢失调相关疾病中的作用，以及周脂素是否可被视为癌症和肥胖症的潜在治疗靶点。
