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Am J Physiol Endocrinol Metab 292: E1637-E1646, 2007. First published February 6, 2007; doi:10.1152/ajpendo.00670.2006
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Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation

Yaguang Si,1 Jeongah Yoon,2 and Kyongbum Lee2

Departments of 1Biology and 2Chemical and Biological Engineering, Tufts University, Medford, Massachusetts

Submitted 8 December 2006 ; accepted in final form 31 January 2007

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.

adipocyte metabolism; metabolic profile; network modularity


Address for reprint requests and other correspondence: K. Lee, Dept. of Chemical and Biological Engineering, Tufts Univ., 4 Colby St., Rm. 142, Medford, MA 02155 (e-mail: kyongbum.lee{at}tufts.edu)






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