Banfi Cristina, Mallia Alice, Ghilardi Stefania, Brioschi Maura, Gianazza Erica, Eligini Sonia, Sahlén Pelin, Baetta Roberta
Centro Cardiologico Monzino IRCCS, Unit of Functional Proteomics, Metabolomics, and Network Analysis, 20138 Milan, Italy.
Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", Università di Pavia, 27100 Pavia, Italy.
Antioxidants (Basel). 2023 Feb 21;12(3):542. doi: 10.3390/antiox12030542.
The process of adipogenesis involves the differentiation of preadipocytes into mature adipocytes. Excessive adipogenesis promotes obesity, a condition that increasingly threatens global health and contributes to the rapid rise of obesity-related diseases. We have recently shown that prenylcysteine oxidase 1 (PCYOX1) is a regulator of atherosclerosis-disease mechanisms, which acts through mechanisms not exclusively related to its pro-oxidant activity. To address the role of PCYOX1 in the adipogenic process, we extended our previous observations confirming that Pcyox1/Apoe mice fed a high-fat diet for 8 or 12 weeks showed significantly lower body weight, when compared to Pcyox1/Apoe mice, due to an evident reduction in visceral adipose content. We herein assessed the role of PCYOX1 in adipogenesis. Here, we found that PCYOX1 is expressed in adipose tissue, and, independently from its pro-oxidant enzymatic activity, is critical for adipogenesis. gene silencing completely prevented the differentiation of 3T3-L1 preadipocytes, by acting as an upstream regulator of several key players, such as FABP4, PPARγ, C/EBPα. Proteomic analysis, performed by quantitative label-free mass spectrometry, further strengthened the role of PCYOX1 in adipogenesis by expanding the list of its downstream targets. Finally, the absence of reduces the inflammatory markers in adipose tissue. These findings render PCYOX1 a novel adipogenic factor with possible pathophysiological or therapeutic potential.
脂肪生成过程涉及前脂肪细胞分化为成熟脂肪细胞。过度的脂肪生成会导致肥胖，这一状况日益威胁全球健康，并促使肥胖相关疾病迅速增加。我们最近发现，异戊烯基半胱氨酸氧化酶1（PCYOX1）是动脉粥样硬化疾病机制的调节因子，其作用机制并非完全与其促氧化活性相关。为了探究PCYOX1在脂肪生成过程中的作用，我们扩展了之前的观察结果，证实喂食高脂饮食8周或12周的Pcyox1/Apoe小鼠与Pcyox1/Apoe小鼠相比，体重显著降低，这是由于内脏脂肪含量明显减少。我们在此评估了PCYOX1在脂肪生成中的作用。在这里，我们发现PCYOX1在脂肪组织中表达，并且独立于其促氧化酶活性，对脂肪生成至关重要。基因沉默通过作为几个关键因子（如脂肪酸结合蛋白4、过氧化物酶体增殖物激活受体γ、CCAAT/增强子结合蛋白α）的上游调节因子，完全阻止了3T3-L1前脂肪细胞的分化。通过无标记定量质谱进行的蛋白质组学分析，通过扩充其下游靶点列表，进一步强化了PCYOX1在脂肪生成中的作用。最后，PCYOX1的缺失降低了脂肪组织中的炎症标志物。这些发现使PCYOX1成为一种具有潜在病理生理学或治疗潜力的新型脂肪生成因子。
