Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis [Methods]

The brain is highly enriched in the long-chain omega-3 (n-3) PUFA DHA. Due to the limited capacity for local DHA synthesis in the brain, it relies on a continual supply from the circulation to replenish metabolized DHA. Previous studies investigating brain DHA turnover and metabolism have relied on isotope tracers to determine brain fatty acid kinetics; however, this approach is cumbersome and costly. We applied natural abundance carbon isotope ratio analysis via high-precision gas chromatography combustion isotope ratio mass spectrometry, without the use of labeled tracers, to determine the half-life of brain DHA in mice following a dietary switch experiment. Mice fed diets containing either α-linolenic acid (ALA) or DHA as the sole dietary n-3 PUFA were switched onto diets containing ALA, DHA, or ALA + DHA at 6 weeks of age, while control mice were maintained on their respective background diet. We measured brain DHA carbon isotope ratios (reported as 13CDHA signatures) over a 168-day time course. Brain 13CDHA signatures of control mice maintained on background diets over the time course were stable (P > 0.05). Brain 13CDHA signatures of mice switched to the DHA or ALA + DHA diet from the ALA diet changed over time, yielding brain incorporation half-lives of 40 and 34 days, respectively. These half-lives determined by natural abundance carbon isotope ratio analysis were consistent with estimates from kinetic isotope tracer studies. Our results demonstrate the feasi...
Source: The Journal of Lipid Research - Category: Lipidology Authors: Tags: Methods Source Type: research