Inhibition of nucleotide biosynthesis disrupts lipid accumulation and adipogenesis.
Inhibition of nucleotide biosynthesis disrupts lipid accumulation and adipogenesis.
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DOI：
10.1016/j.jbc.2023.104635
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发表时间：
2023-05
影响因子：
4.8
通讯作者：
Zaganjor, Elma
中科院分区：
文献类型：
--
作者：
Shinde, Abhijit B.;Nunn, Elizabeth R.;Wilson, Genesis A.;Chvasta, Mathew T.;Pinette, Julia A.;Myers, Jacob W.;Peck, Sun H.;Spinelli, Jessica B.;Zaganjor, Elma
能量平衡和营养供应是细胞决定保持静止、增殖或分化成成熟细胞的关键决定因素。在评估其环境状态后，细胞必须重新调整其代谢以支持不同的细胞结果。从机制上讲，代谢物如何调节细胞命运的决定是知之甚少。我们使用脂肪形成作为我们的模型系统，以确定代谢在分化中的作用。我们分离出脂肪组织间质血管部分细胞，并在成脂分化前后分析代谢产物，以确定与这些不同细胞状态相关的代谢特征。我们发现，分化改变核苷酸积累。此外，核苷酸生物合成的抑制阻止脂肪细胞内的脂质储存，并下调脂肪生成因子的表达。与增殖细胞相反，其中雷帕霉素复合物1的机制靶点被嘌呤积累激活，雷帕霉素复合物1信号传导的机制靶点不受分化脂肪细胞中嘌呤水平的影响。相反，我们的数据表明，嘌呤调节脂肪生成的转录激活因子，过氧化物酶体增殖物激活受体γ和CCAAT/增强子结合蛋白α，以促进分化。虽然从头核苷酸的生物合成主要是在增殖中研究，我们的研究指出，它在脂肪细胞分化的要求。
Energy balance and nutrient availability are key determinants of cellular decisions to remain quiescent, proliferate, or differentiate into a mature cell. After assessing its environmental state, the cell must rewire its metabolism to support distinct cellular outcomes. Mechanistically, how metabolites regulate cell fate decisions is poorly understood. We used adipogenesis as our model system to ascertain the role of metabolism in differentiation. We isolated adipose tissue stromal vascular fraction cells and profiled metabolites before and after adipogenic differentiation to identify metabolic signatures associated with these distinct cellular states. We found that differentiation alters nucleotide accumulation. Furthermore, inhibition of nucleotide biosynthesis prevented lipid storage within adipocytes and downregulated the expression of lipogenic factors. In contrast to proliferating cells, in which mechanistic target of rapamycin complex 1 is activated by purine accumulation, mechanistic target of rapamycin complex 1 signaling was unaffected by purine levels in differentiating adipocytes. Rather, our data indicated that purines regulate transcriptional activators of adipogenesis, peroxisome proliferator–activated receptor γ and CCAAT/enhancer-binding protein α, to promote differentiation. Although de novo nucleotide biosynthesis has mainly been studied in proliferation, our study points to its requirement in adipocyte differentiation.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
8.9
作者：
Hardie DG
通讯作者：
Hardie DG
影响因子：
5.3
作者：
Kim, Sun-Joong;Tang, Tianyi;Sul, Hei Sook
通讯作者：
Sul, Hei Sook
DOI：
10.1111/j.1432-1033.1990.tb15293.x
发表时间：
1990-01-12
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
DAVIES, SP;SIM, ATR;HARDIE, DG
通讯作者：
HARDIE, DG
影响因子：
16
作者：
Rosen, ED;Sarraf, P;Mortensen, RM
通讯作者：
Mortensen, RM