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2H2O incorporation into hepatic acetyl‐CoA and de novo lipogenesis as measured by Krebs cycle‐mediated 2H‐enrichment of glutamate and glutamine

Deuterated water is widely used for measuring de novo lipogenesis on the basis of quantifying lipid 2H‐enrichment relative to that of body water. However, incorporation of 2H‐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 2H nuclear magnetic resonance analysis of hepatic glutamate/glutamine (Glx) enrichment and triglyceride methyl enrichment was directly determined by 2H nuclear magnetic resonance of triglycerides. Acetyl‐CoA 2H‐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, 2011. © 2011 Wiley Periodicals, Inc.