Mfsd2a and Glut1 Brain Nutrient Transporters Expression Increase with 32-Week Low and High Lard Compared with Fish-Oil Dietary Treatment in C57Bl/6 Mice

BACKGROUND: Diet-mediated alterations of critical brain nutrient transporters, major facilitator super family domain-containing 2a (Mfsd2a) and glucose transporter 1 (Glut1), have wide reaching implications in brain health and disease. OBJECTIVE: The aim of the study was to examine the impact of long-term low- and high-fat diets with lard or fish oil on critical brain nutrient transporters, Mfsd2a and Glut1. METHODS: Eight-week-old male C57BL/6 mice were fed 1 of the following 4 diets for 32 wk: 10% of kcal from lard, 10% of kcal from fish oil, 41% of kcal from lard, or 41% of kcal from fish oil. Body weight and blood chemistries delineated dietary effects. Cortical and subcortical Mfsd2a and Glut1 mRNA and protein expression were evaluated, with other supportive nutrient-sensitive targets also assessed for mRNA expression changes. RESULTS: Fish-oil diets increased cortical Mfsd2a mRNA expression compared with lard diets. Subcortical Mfsd2a mRNA expression decreased as the percentage of fat in the diet increased. There was an interaction between the type and percentage of fat with cortical and subcortical Mfsd2a and cortical Glut1 protein expression. In the lard diet groups, protein expression of cortical and subcortical Mfsd2a and cortical Glut1 significantly increased as fat percentage increased. As the fat percentage increased in the fish-oil diet groups, protein expression of cortical and subcortical Mfsd2a and cortical Glut1 did not change. When comparing the fish-oil groups with 10% lard, cortical Mfsd2a protein expression was significantly higher in the 10% and 41% fish-oil groups, whereas cortical Glut1 protein expression was significantly higher in only the 10% fish-oil group. A positive correlation between cortical peroxisome proliferator–activated receptor γ mRNA expression and Mfsd2a protein expression was shown. CONCLUSION: Corresponding to chronic dietary treatment, an interaction between the type of fat and the percentage of fat exists respective to changes in brain expression of the key nutrient transporters Mfsd2a and Glut1.