Zonation of Labeling of Lipogenic Acetyl-CoA across the Liver
Measurement of fractional lipogenesis by condensation polymerization methods assumes constant enrichment of lipogenic acetyl-CoA in all hepatocytes. mass isotopomer distribution analysis (MIDA) and isotopomer spectral analysis (ISA) represent such methods and are based on the combinatorial analyses...
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Veröffentlicht in: | The Journal of biological chemistry 2004-10, Vol.279 (41), p.43207-43216 |
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Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Measurement of fractional lipogenesis by condensation polymerization methods assumes constant enrichment of lipogenic acetyl-CoA
in all hepatocytes. mass isotopomer distribution analysis (MIDA) and isotopomer spectral analysis (ISA) represent such methods
and are based on the combinatorial analyses of mass isotopomer distributions (MIDs) of fatty acids and sterols. We previously
showed that the concentration and enrichment of [ 13 C]acetate decrease markedly across the dog liver because of the simultaneous uptake and production of acetate. To test for
zonation of the enrichment of lipogenic acetyl-CoA, conscious dogs, prefitted with transhepatic catheters, were infused with
glucose and [1,2- 13 C 2 ]acetate in a branch of the portal vein. Analyses of MIDs of fatty acids and sterols isolated from liver, bile, and plasma
very low density lipoprotein by a variant of ISA designed to detect gradients in precursor enrichment revealed marked zonation
of enrichment of lipogenic acetyl-CoA. As control experiments where no zonation of acetyl-CoA enrichment would be expected,
isolated rat livers were perfused with 10 m m [1,2- 13 C 2 ]acetate. The ISA analyses of MIDs of fatty acids and sterols from liver and bile still revealed a zonation of acetyl-CoA
enrichment. We conclude that zonation of hepatic acetyl-CoA enrichment occurs under a variety of animal models and physiological
conditions. Failure to consider gradients of precursor enrichment can lead to underestimations of fractional lipogenesis calculated
from the mass isotopomer distributions. The degree of such underestimation was modeled in vitro , and the data are reported in the companion paper (Bederman, I. R., Kasumov, T., Reszko, A. E., David, F., Brunengraber,
H., and Kelleher, J. K. (2004) J. Biol. Chem. 279, 43217-43226). |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M403838200 |