(H2O)-H-2 Incorporation Into Hepatic Acetyl-CoA and De novo Lipogenesis as Measured by Krebs Cycle-Mediated H-2-Enrichment of Glutamate and Glutamine

作者：Silva Ana Maria; Martins Fatima; Jones John G^*; Carvalho Rui

来源：Magnetic Resonance in Medicine, 2011, 66(6): 1526-1530.

DOI：10.1002/mrm.22955

• fatty acyl CoA synthase
• hepatic triglyceride
• deuterium exchange

Deuterated water is widely used for measuring de novo lipogenesis on the basis of quantifying lipid H-2-enrichment relative to that of body water. However, incorporation of H-2-enrichment from body water into newly synthesized lipid molecules is incomplete therefore the true lipid precursor enrichment differs from that of body water. We describe a novel measurement of de novo lipogenesis that is based on a true precursor-product analysis of hepatic acetyl-CoA and triglyceride methyl enrichments from deuterated water. After deuterated water administration to seven in situ and seven perfused livers, acetyl-CoA methyl enrichment was inferred from H-2 nuclear magnetic resonance analysis of hepatic glutamate/glutamine (Glx) enrichment and triglyceride methyl enrichment was directly determined by H-2 nuclear magnetic resonance of triglycerides. Acetyl-CoA H-2-enrichment was 71% +/- 1% that of body water for in situ livers and 53% +/- 2% of perfusate water for perfused livers. From the ratio of triglyceride-methyl/acetyl-CoA enrichments, fractional de novo lipogenesis rates of 0.97% +/- 0.09%/2 hr and 7.92% +/- 1.47%/48 hr were obtained for perfused and in situ liver triglycerides, respectively. Our method reveals that acetyl-CoA enrichment is significantly less than body water both for in situ and perfused livers. Furthermore, the difference between acetyl-CoA and body water enrichments is sensitive to the experimental setting. Magn Reson Med 66:1526-1530, 2011.

• 出版日期2011-12