Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520300213 |
| _version_ | 1818726393010192384 |
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| author | R.J. Scott Lacombe Chi-Chiu Lee Richard P. Bazinet |
| author_facet | R.J. Scott Lacombe Chi-Chiu Lee Richard P. Bazinet |
| author_sort | R.J. Scott Lacombe |
| collection | DOAJ |
| description | 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 δ13CDHA signatures) over a 168-day time course. Brain δ13CDHA signatures of control mice maintained on background diets over the time course were stable (P > 0.05). Brain δ13CDHA 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 feasibility of natural abundance carbon isotope ratio analysis in the study of fatty acid metabolism without the use of isotopically labeled fatty acid tracers. |
| first_indexed | 2024-12-17T21:57:29Z |
| format | Article |
| id | doaj.art-d04713e414d6412ca2ce9d8741a7f464 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T21:57:29Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-d04713e414d6412ca2ce9d8741a7f4642022-12-21T21:31:04ZengElsevierJournal of Lipid Research0022-22752020-01-01611116126Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysisR.J. Scott Lacombe0Chi-Chiu Lee1Richard P. Bazinet2Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, CanadaDepartment of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, CanadaTo whom correspondence should be addressed; Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, CanadaThe 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 δ13CDHA signatures) over a 168-day time course. Brain δ13CDHA signatures of control mice maintained on background diets over the time course were stable (P > 0.05). Brain δ13CDHA 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 feasibility of natural abundance carbon isotope ratio analysis in the study of fatty acid metabolism without the use of isotopically labeled fatty acid tracers.http://www.sciencedirect.com/science/article/pii/S0022227520300213lipidsomega-3metabolismdietdocosahexaenoic acidmass spectrometry |
| spellingShingle | R.J. Scott Lacombe Chi-Chiu Lee Richard P. Bazinet Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis Journal of Lipid Research lipids omega-3 metabolism diet docosahexaenoic acid mass spectrometry |
| title | Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis |
| title_full | Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis |
| title_fullStr | Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis |
| title_full_unstemmed | Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis |
| title_short | Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis |
| title_sort | turnover of brain dha in mice is accurately determined by tracer free natural abundance carbon isotope ratio analysis |
| topic | lipids omega-3 metabolism diet docosahexaenoic acid mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520300213 |
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