William Yakah1, Pratibha Singh2, George Perides2, Joanne Brown2, Steven D Freedman2,3, Camilia R Martin3,4. 1. Department of Neuroscience, Michigan State University, East Lansing, MI. 2. Division of Gastroenterology, Boston, MA. 3. Division of Translational Research, Boston, MA. 4. Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA.
Abstract
BACKGROUND: Developmental expression of fatty acid transporters and their role in polyunsaturated fatty acid concentrations in the postnatal period have not been evaluated. OBJECTIVE: We hypothesized that transporter expression is developmentally regulated, tissue-specific, and that expression can modulate fatty acid accretion independently of diet. METHODS: Brain and lung transporter expression were quantified in C57BL/6 wild-type (WT) and Fat1 mice. Pups were dam-fed until day 21. Dams were fed AIN-76A 10% corn oil to represent a typical North American/European diet. After weaning, mice were fed the same diet as dams. Gene expression of Fatp1, Fatp4, Fabp5, and Fat/cd36 was quantified by quantitative reverse transcriptase-polymerase chain reaction. Fatty acid concentrations were measured by GC-MS. RESULTS: Brain docosahexaenoic acid (DHA) concentrations increased from day 3 to day 28 in both genotypes, with higher concentrations at days 3 and 14 in Fat1 than in WT mice [median (IQR)]: 10.7 (10.6-11.2) mol% compared with 6.6 (6.4-7.2) mol% and 12.5 (12.4-12.9) mol% compared with 8.9 (8.7-9.1) mol%, respectively; P < 0.05). During DHA accrual, transporter expression decreased. Fold changes in brain Fatp4, Fabp5, and Fat/cd36 were inversely correlated with fold changes in brain DHA concentrations in Fat1 relative to WT mice (ρ = -0.85, -0.75, and -0.78, respectively; P ≤ 0.001). Lung DHA concentrations were unchanged across the 3 time points for both genotypes. Despite unchanging DHA concentrations, there was increased expression of Fatp1 at days 14 and 28 (5-fold), Fatp4 at day 14 (2.3-fold), and Fabp5 at day 14 (3.8-fold) relative to day 3 in Fat1 mice. In WT mice, Fatp1 increased almost 5-fold at day 28 relative to day 3. There was no correlation between lung transporters and DHA concentrations in Fat1 relative to WT mice. CONCLUSIONS: Development of fatty acid transporter expression in C57BL/6 WT and Fat1 mice is genotype and tissue specific. Further, postnatal accretion of brain DHA appears independent of transporter status, with tissue concentrations representing dietary contributions.
BACKGROUND: Developmental expression of fatty acid transporters and their role in polyunsaturated fatty acid concentrations in the postnatal period have not been evaluated. OBJECTIVE: We hypothesized that transporter expression is developmentally regulated, tissue-specific, and that expression can modulate fatty acid accretion independently of diet. METHODS: Brain and lung transporter expression were quantified in C57BL/6 wild-type (WT) and Fat1mice. Pups were dam-fed until day 21. Dams were fed AIN-76A 10% corn oil to represent a typical North American/European diet. After weaning, mice were fed the same diet as dams. Gene expression of Fatp1, Fatp4, Fabp5, and Fat/cd36 was quantified by quantitative reverse transcriptase-polymerase chain reaction. Fatty acid concentrations were measured by GC-MS. RESULTS: Brain docosahexaenoic acid (DHA) concentrations increased from day 3 to day 28 in both genotypes, with higher concentrations at days 3 and 14 in Fat1 than in WT mice [median (IQR)]: 10.7 (10.6-11.2) mol% compared with 6.6 (6.4-7.2) mol% and 12.5 (12.4-12.9) mol% compared with 8.9 (8.7-9.1) mol%, respectively; P < 0.05). During DHA accrual, transporter expression decreased. Fold changes in brain Fatp4, Fabp5, and Fat/cd36 were inversely correlated with fold changes in brain DHA concentrations in Fat1 relative to WT mice (ρ = -0.85, -0.75, and -0.78, respectively; P ≤ 0.001). Lung DHA concentrations were unchanged across the 3 time points for both genotypes. Despite unchanging DHA concentrations, there was increased expression of Fatp1 at days 14 and 28 (5-fold), Fatp4 at day 14 (2.3-fold), and Fabp5 at day 14 (3.8-fold) relative to day 3 in Fat1mice. In WT mice, Fatp1 increased almost 5-fold at day 28 relative to day 3. There was no correlation between lung transporters and DHA concentrations in Fat1 relative to WT mice. CONCLUSIONS: Development of fatty acid transporter expression in C57BL/6 WT and Fat1mice is genotype and tissue specific. Further, postnatal accretion of brain DHA appears independent of transporter status, with tissue concentrations representing dietary contributions.
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