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

Mackenzie E. Smith, Chuck T. Chen, Chiraag A. Gohel, Giulia Cisbani, Daniel K. Chen, Kimia Rezaei, Andrew McCutcheon and Richard P. Bazinet ()
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Mackenzie E. Smith: University of Toronto
Chuck T. Chen: University of Toronto
Chiraag A. Gohel: George Washington University
Giulia Cisbani: University of Toronto
Daniel K. Chen: University of Toronto
Kimia Rezaei: University of Toronto
Andrew McCutcheon: University of Toronto
Richard P. Bazinet: University of Toronto

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract 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. In this work, we use naturally occurring carbon isotope ratios (13C/12C; δ13C) to uncover the origin of brain PAM at postnatal days 0, 10, 21 and 35, and RNA sequencing to identify the pathways involved in maintaining brain PAM, at day 35, in mice fed diets with low, medium, and high PAM from birth. Here we show that DNL from dietary sugars maintains the majority of brain PAM during development and is augmented in mice fed low PAM. Importantly, the upregulation of hepatic DNL genes, in response to low PAM at day 35, demonstrates the presence of a compensatory mechanism to maintain total brain PAM pools compared to the liver; suggesting the importance of brain PAM regulation.

Date: 2024
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DOI: 10.1038/s41467-023-44388-4

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