Upregulated hepatic lipogenesis from dietary sugars in response to low palmitate feeding supplies brain palmitate

Palmitic acid (PAM) can be provided in the diet or synthesized via de novo lipogenesis (DNL), primarily from glucose. Preclinical work on the origin of brain PAM during development is scarce and contrasts results in adults. Using naturally occurring carbon isotope ratios (13C/12C; δ13C) we investigated the origin of brain PAM at postnatal days 0, 10, 21 and 35 in mice fed low, medium, and high PAM diets from birth, and performed RNA sequencing at day 35 to identify pathways involved in maintaining brain PAM. We show that DNL from dietary sugars maintains the majority of brain PAM during development and is augmented in mice fed low PAM. Hepatic DNL genes were upregulated in response to low PAM at day 35, indicating a compensatory mechanism to maintain total brain PAM pools compared to the liver, underscoring the importance of brain PAM regulation.