The Majority of Brain Palmitic Acid is Maintained by Lipogenesis from Dietary Sugars and is Augmented in Mice fed Low Palmitic Acid Levels from Birth.

Previously, results from studies investigating if brain palmitic acid (16:0; PAM) was maintained by either dietary uptake or lipogenesis de novo (DNL) varied. Here, we utilize naturally occurring carbon isotope ratios (13 C/12 C; δ13 C) to uncover the origin of brain PAM. Additionally, we explored brain and liver fatty acid concentration, total brain metabolomic profile, and behaviour. BALB/c dams were equilibrated onto either a low PAM diet (LP; 95%) prior to producing one generation of offspring. Offspring stayed on the respective diet of the dam until 15-weeks of age, at which time the Open Field test was conducted in the offspring, prior to euthanasia and tissue lipid extraction. Although liver PAM was lower in offspring fed the LP diet, as well as female offspring, brain PAM was not affected by diet or sex. Across offspring of either sex on both diets, brain 13 C-PAM revealed compared to dietary uptake, DNL from dietary sugars contributed 68.8%-79.5% and 46.6%-58.0% to the total brain PAM pool by both peripheral and local brain DNL, and local brain DNL alone, respectively. DNL was augmented in offspring fed the LP diet, and the ability to upregulate DNL in the liver or the brain depended on sex. Anxiety-like behaviours were decreased in offspring fed the LP diet and were correlated with markers of LP diet consumption including increased liver 13 C-PAM, warranting further investigation. Altogether, our results indicate that DNL from dietary sugars is a compensatory mechanism to maintain brain PAM in response to a LP diet.