Natural Abundance Carbon Isotopic Analysis Indicates the Equal Contribution of Local Synthesis and Plasma Uptake to Palmitate Levels in the Mouse Brain

Saturated fatty acids are the most abundant fatty acids in the brain, however, there has been some debate regarding the ability of intact dietary saturated fatty acids to be incorporated into the brain. In the present study, we use compound specific isotope analysis to measure the natural abundance carbon isotopic signature of brain, liver, and blood palmitic acid (PAM) and compare it to the dietary PAM and sugar isotopic signatures to calculate the relative contribution of both the incorporation of intact and endogenously synthesized PAM to these pools. Mice were equilibrated to the study diet, and extracted fatty acids were analyzed with gas chromatography isotope ratio mass spectrometry to determine the carbon isotopic signature of PAM (δ¹³C_PAM). Liver, serum total, and serum unesterified fatty acid δ¹³C_PAM ranged between ?20.6 and ?21.1 mUr and were approximately 8.5 mUr more enriched in ¹³C when compared to the dietary PAM signature. Brain δ¹³C_PAM was found to be more enriched than liver or blood pools (?16.7 ± 0.2 mUr, mean ± SD). Two end‐member‐mixed modeling using the carbon isotopic signature of dietary PAM and dietary sugars determined the contribution of synthesis to the total tissue PAM pool to range between 44% and 48%. This suggests that endogenous synthesis and dietary PAM are near equal contributors to brain, liver, and blood PAM pools. In conclusion, our data provide evidence that brain PAM levels are maintained by both local endogenous synthesis and through the uptake of intact PAM from the blood.