Whole Body Synthesis-Secretion Rates of Long-Chain n-3 Polyunsaturated Fatty Acids from Circulating Unesterified α-Linolenic Acid in Unanesthetized Rats

Docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n- 3), long-chain n-3 polyunsaturated fatty acids (PUFAs),  considered important for brain and heart function, can be obtained directly from fish products in the diet or from synthesis in the liver from diet-derived α-linolenic acid (α-LNA, 18:3n-3) by desaturation and elongation steps. The daily human dietary requirement of DHA plus EPA is not agreed upon, and their rates of liver synthesis in humans and nonhumans are not known. In this paper, we estimated whole body (presumably  liver) synthesis rates in the rat. [U-13C]α-LNA was infused intravenously in unanesthetized adult male rats for 2 h, and labeled and unlabeled n-3 PUFAs in arterial plasma were measured using negative chemical ionization gas chromatography mass spectrometry (NCI-GC/MS). Newly synthesized esterified [13C]DHA, [13C]EPA and [13C]DPA were detected in arterial plasma after 60 min of infusion, after which their  concentrations rose in an approximate S-shaped manner. Plasma esterified concentration x plasma volume data were fit with a sigmoidal  equation, whose peak first derivatives provided synthesis-secretion rates of EPA, DPA and DHA equal to 8.40, 6.27, and 9.84 μmol/day,  respectively. The DHA synthesis rate exceeded the published daily rat brain DHA consumption rate by 30-fold, which suggests that liver synthesis from α-LNA could maintain brain DHA homeostasis were DHA absent from the diet. This stable-isotope intravenous infusion method using 13C-labeled PUFAs might be extended for use in human subjects. Author's Abstract.