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Am J Physiol Endocrinol Metab 277: E1022-E1027, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 6, E1022-E1027, December 1999

Zonation of acetate labeling across the liver: implications for studies of lipogenesis by MIDA

Michelle A. Puchowicz1, Ilya R. Bederman1, Blandine Comte1, Dawei Yang1, France David1, Eric Stone2, Kareem Jabbour2, David H. Wasserman3, and Henri Brunengraber1

1 Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106; and Departments of 2 Surgery and 3 Molecular Physiology/Biophysics, Vanderbilt University, Nashville, Tennessee 37232

Measurement of fractional lipogenesis by mass isotopomer distribution analysis (MIDA) of fatty acids or cholesterol labeled from [13C]acetate assumes constant enrichment of lipogenic acetyl-CoA in all hepatocytes. This would not be the case if uptake and release of acetate by the liver resulted in transhepatic gradients of acetyl-CoA enrichment. Conscious dogs, prefitted with transhepatic catheters, were infused with glucose and [1,2-13C2]acetate. Stable concentrations and enrichments of acetate were measured in artery (17 µM, 36%), portal vein (61 µM, 5.4%), and hepatic vein (17 µM, 1.0%) and were computed for mixed blood entering the liver (53 µM, 7.4%). We also measured balances of propionate and butyrate across gut and liver. All gut release of propionate and butyrate is taken up by the liver. The threefold decrease in acetate concentration and the sevenfold decrease in acetate enrichment across the liver strongly suggest that the enrichment of lipogenic acetyl-CoA decreases across the liver. Thus fractional hepatic lipogenesis measured in vivo by MIDA may be underestimated.

acetyl-coenzyme A; mass spectrometry; fatty acid synthesis; cholesterol synthesis


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