Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation
Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation
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DOI：
10.1152/ajpendo.00670.2006
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发表时间：
2007-06-01
影响因子：
5.1
通讯作者：
Lee, Kyongbum
中科院分区：
文献类型：
--
作者：
Si, Yaguang;Yoon, Jeongah;Lee, Kyongbum
白色脂肪组织（WAT）质量是肥胖和相关健康风险的主要决定因素。WAT扩增由白色脂肪细胞数量和大小的增加引起，这反过来反映了细胞代谢状态的一系列变化。为了定量分析从头脂肪细胞形成过程中发生的代谢变化，代谢通量分析（MFA）结合一种新的模块化分析算法用于区分3 T3- L1前脂肪细胞。还评估了使用I型胶原凝胶作为有效的长期培养基质。计算的通量分布预测了几种细胞内跨隔室途径的顺序激活，包括脂肪生成、戊糖磷酸途径和苹果酸循环，与早期的同位素示踪实验和基因分析研究非常一致。将脂肪细胞代谢网络划分为高度相互作用的反应亚组表明了与脂肪细胞的脂质负载表型一致的主要途径的功能重组。通量和模块性分析结果一起指出丙酮酸周围的通量分布是脂肪细胞脂质积累的关键指标。
White adipose tissue ( WAT) mass is the main determinant of obesity and associated health risks. WAT expansion results from increases in white adipocyte cell number and size, which in turn reflect a series of shifts in the cellular metabolic state. To quantitatively profile the metabolic alterations occurring during de novo adipocyte formation, metabolic flux analysis ( MFA) was used in conjunction with a novel modularity analysis algorithm on differentiating 3T3- L1 preadipocytes. Use of a type I collagen gel as an effective long- term culture substrate was also assessed. The calculated flux distributions predicted the sequential activation of several intracellular cross- compartmental pathways, including lipogenesis, the pentose phosphate pathway, and the malate cycle, in good agreement with earlier isotopic tracer experiments and gene profiling studies. Partition of the adipocyte metabolic network into highly interacting reaction subgroups suggested a functional reorganization of the major pathways consistent with the lipid- loading phenotype of the adipocyte. Flux and modularity analysis results together point to the flux distribution around pyruvate as a key indicator of adipocyte lipid accumulation.