Tissue-Specific Regulation of Postprandial Non-Esterified Fatty Acid Metabolism in individuals with prediabetes
After a meal, it is generally assumed that tissue non-esterified fatty acids (NEFA) uptake falls in proportion of the reduction of systemic NEFA appearance from insulin-mediated suppression of adipose tissue lipolysis. Here, we combined dynamic [11C]palmitate PET/CT, stable isotope tracers, and MRI to measure palmitate uptake, oxidation, and esterification in the heart, liver, skeletal muscle, and subcutaneous and visceral adipose tissue, in the fasted state and 60min after a mixed meal in individuals with prediabetes. Net palmitate uptake decreased in all tissues, but most tissues extracted a larger fraction of circulating palmitate after the meal. The intracellular fate of palmitate differed between organs. The heart shifted toward oxidation, the liver toward esterification, maintaining VLDL-palmitate release, and this shift was smaller in individuals with more liver fat. Both adipose depots increased fractional esterification, and visceral fat almost stopped releasing palmitate. Thus, plasma NEFA overestimates the postprandial reduction in lean tissue NEFA exposure.
Authors
- Jean‐Pierre Després (ORCID: https://orcid.org/0000-0002-5193-583X)
- Gabriel Mary Richard (ORCID: https://orcid.org/0000-0002-5195-4870)
- Femke Rutters (ORCID: https://orcid.org/0000-0002-1008-678X)
- Warner Mbuila Mampuya (ORCID: https://orcid.org/0000-0003-0994-932X)
- Brigitte Guérin (ORCID: https://orcid.org/0000-0002-0319-4512)
- Denis P. Blondin (ORCID: https://orcid.org/0000-0001-6805-0985)
- Christophe Noll (ORCID: https://orcid.org/0000-0002-2874-2060)
- L Dumont (ORCID: https://orcid.org/0000-0002-7681-6212)
- André C. Carpentier (ORCID: https://orcid.org/0000-0002-3983-8156)
- Joris Hoeks J (ORCID: https://orcid.org/0000-0002-0265-0870)
- Sophie Hogan‐Lamarre
- Otman Sarrhini (ORCID: https://orcid.org/0000-0001-6231-2630)
- Elisa Le Roux (ORCID: https://orcid.org/0000-0001-5126-4848)
- Serge Phoenix (ORCID: https://orcid.org/0009-0003-5697-0655)
- Mélanie Fortin (ORCID: https://orcid.org/0000-0002-7265-5079)
- Patrick Schrauwen (ORCID: https://orcid.org/0000-0002-0973-847X)
- Lucie Bouffard
- Frédérique Frisch
- Parminder Raina (ORCID: https://orcid.org/0000-0002-8107-3193)
- MARIE LEPITRE
- ÉRIC TURCOTTE
Institutions
- Université de Sherbrooke (CA)
- Maastricht University (NL)
- Amsterdam Public Health (NL)
- Deutsches Diabetes-Zentrum e.V. (DE)
- Université Laval (CA)
- Centre de recherche du CHUS (CA)
- Heinrich Heine University Düsseldorf (DE)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- McMaster University (CA)
Publication Details
- Journal
- medRxiv
- Published
- 2026-10-26
- DOI
- https://doi.org/10.64898/2026.10.23.26365753
- Primary Topic
- Lipid metabolism and biosynthesis
- Type
- preprint
Funders
- Diabetes Fonds
- Canadian Institutes of Health Research