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 de novo lipogenesis (DNL) varied. Here, we utilize naturally occurring carbon isotope ratios (C-13/C-12; delta C-13) to uncover the origin of brain PAM. Additionally, we explored brain and liver fatty acid concentration, brain metabolomics, and behavior. BALB/c dams were equilibrated onto either a low PAM diet (LP; <2%) or high PAM diet (HP; >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, prior to euthanasia and tissue lipid extraction. Although liver PAM was lower in mice fed the LP diet, as well as female mice, brain PAM was not affected by diet or sex. Across mice of either sex on both diets, brain C-13-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 mice fed the LP diet, and the ability to up-regulate DNL in the liver or the brain depended on sex. Anxiety-like behaviors were decreased in mice fed the LP diet and were correlated with markers of LP diet consumption including increased liver C-13-PAM, warranting further investigation. Altogether, our results indicate that DNL from dietary sugars is a compensatory mechanism to maintain brain PAM in response to the LP diet.

Automated summary

The study revealed that de novo lipogenesis from dietary sugars is a compensatory mechanism to maintain brain palmitic acid, especially under low PAM diet conditions. Additionally, there were differences in the ability to regulate DNL in the liver and brain based on sex, while anxiety-like behaviors were correlated with markers of LP diet consumption.