Utilization of Uniformly Labeled ¹³C‐Polyunsaturated Fatty Acids in the Synthesis of Long‐Chain Fatty Acids and Cholesterol Accumulating in the Neonatal Rat Brain

Abstract

Polyunsaturated fatty acids are needed for normal neonatal brain development, but the degree of conversion of the 18‐carbon polyunsaturated fatty acid precursors consumed in the diet to their respective 20‐and 22‐carbon polyunsaturates accumulating in the brain is not well known. In the present study, in vivo 13C nuclear magnetic resonance spectroscopy was used to monitor noninvasively the brain uptake and metabolism of a mixture of uniformly 13C‐enriched 16‐and 18‐carbon polyunsaturated fatty acid methyl esters injected intragastrically into neonatal rats. In vivo NMR spectra of the rat brain at postnatal days 10 and 17 had larger fatty acid signals than in uninjected controls, but changes in levels of individual fatty acids could not be distinguished. One day after injection of the U‐13C‐polyunsaturated fatty acid mixture, 13C enrichment (measured by isotope ratio mass spectrometry) was similar in brain phospholipids, free fatty acids, free cholesterol, and brain aqueous extract; 13C enrichment remained high in the phospholipids and cholesterol for 15 days. 13C enrichment was similar in the main fatty acids of the brain within 1 day of injection but 15 days later had declined in all except arachidonic acid while continuing to increase in docosahexaenoic acid. These changes in 13C enrichment in brain fatty acids paralleled the developmental changes in brain fatty acid composition. We conclude that, in the neonatal rat brain, dietary 16‐and 18‐carbon polyunsaturates are not only elongated and desaturated but are also utilized for de novo synthesis of long‐chain saturated and monounsaturated fatty acids and cholesterol.

Rapid de-esterification and loss of eicosapentaenoic acid from rat brain phospholipids: an intracerebroventricular study

“…In regards to 14 C-palmitate-infused brains, radiolabeled stearate, palmitoleate, oleate, and 20:1n-9 could originate from desaturation and elongation of infused 14 C-palmitate or the b-oxidation product of 14 C-palmitate, radiolabeled acetyl-CoA. At day 4 post-infusion, cholesterol from both 14 C-palmitate-(4 ± 1 nCi/brain) and 14 C-EPAinfused (3 ± 1 nCi/brain) brains was radiolabeled; thus b-oxidation of palmitate and EPA were confirmed (Cunnane et al 1994). In addition to metabolism via mitochondrial b-oxidation and desaturation/elongation, EPA may have been converted to oxygenated derivatives such as eicosanoids and E-series resolvins and future studies examining this are warranted.…”

“…In regards to 14 C‐palmitate‐infused brains, radiolabeled stearate, palmitoleate, oleate, and 20:1n‐9 could originate from desaturation and elongation of infused 14 C‐palmitate or the β‐oxidation product of 14 C‐palmitate, radiolabeled acetyl‐CoA. At day 4 post‐infusion, cholesterol from both 14 C‐palmitate‐ (4 ± 1 nCi/brain) and 14 C‐EPA‐infused (3 ± 1 nCi/brain) brains was radiolabeled; thus β‐oxidation of palmitate and EPA were confirmed (Cunnane et al. 1994).…”

Altered soluble epoxide hydrolase-derived oxylipins in patients with seasonal major depression: An exploratory study

“…It is unlikely that α-LNA was metabolically utilized for oxylipin synthesis because none of the α- LNA-derived oxylipins changed between seasons. Most likely, α-LNA was metabolically shunted towards increased β-oxidation or recycling into sterols or saturated and monounsaturated fatty acids during winter (Cunnane et al, 2003, 1994; Menard et al, 1998). This possibility along with altered α-LNA intake levels between seasons should be explored in future adequately powered studies.…”

Combination of two fat saturation pulses improves detectability of glucose signals in carbon-13 MR spectroscopy

“…8) The disadvantage of these techniques is the inability to suppress the signals from visceral fat. The following two methods have been employed to suppress lipid signals in 1 H MRS, 1) frequency (chemical shift) selective suppression pulses (CHESS) 9) based on the frequency difference due to the chemical shift, such as those between a proton of water and that of fat, and 2) spatial saturation (SAT) pulses to reduce all signals included in the slab located on the subcutaneous fat layer.…”