Quantitative contributions of diet and liver synthesis to docosahexaenoic acid homeostasis

Dietary requirements for maintaining brain and heart docosahexaenoic acid (DHA, 22:6n-3) homeostasis are not agreed on, in part because rates of liver DHA synthesis from circulating α-linolenic acid (α-LNA, 18:3n-3) have not been quantified. These rates can be estimated using intravenous radiotracer- or heavy isotope-labeled α-LNA infusion. In adult unanesthetized male rats, such infusion shows that liver synthesis–secretion rates of DHA from α-LNA markedly exceed brain and heart DHA synthesis rates and the brain DHA consumption rate, and that liver but not heart or brain synthesis is upregulated when dietary n-3 PUFA content is reduced. These rate differences reflect much higher expression of DHA-synthesizing enzymes in liver, and upregulation of liver but not heart or brain enzyme expression by reduced dietary n-3 PUFA content. A noninvasive intravenous [U−13C]α-LNA infusion method that produces steady-state liver tracer metabolism gives exact liver DHA synthesis–secretion rates and could be extended for human studies.