Tissue-Specific Regulation of Postprandial Non-Esterified Fatty Acid Metabolism in individuals with…

Abstract

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.

HighlightsO_LIAfter a meal, net palmitate uptake fall in all tissues but extraction rises in most C_LIO_LIAfter a meal, the liver directs palmitate toward esterification and the heart toward oxidation C_LIO_LIPlasma NEFA level underestimate lean tissue NEFA exposure after a meal in prediabetes C_LI

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BibTeX

@misc{roux2026tissuespecific,
  title = {{Tissue-Specific Regulation of Postprandial Non-Esterified Fatty Acid Metabolism in individuals with prediabetes}},
  author = {E. Le Roux and S. Hogan-Lamarre and M. Lepitre and F. Frisch and L. Dumont and M. Fortin and G. Richard and C. Noll and O. Sarrhini and W. Mampuya and S. Phoenix and L. Bouffard and B. Guerin and E. Turcotte and F. Rutters and P. Raina and J.-P. Despres and J. Hoeks and P. Schrauwen and A. C. Carpentier and D. P. Blondin},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.23.26365753},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.23.26365753v1},
  note = {CC BY-NC},
}

RIS

TY  - UNPB
TI  - Tissue-Specific Regulation of Postprandial Non-Esterified Fatty Acid Metabolism in individuals with prediabetes
AU  - E. Le Roux
AU  - S. Hogan-Lamarre
AU  - M. Lepitre
AU  - F. Frisch
AU  - L. Dumont
AU  - M. Fortin
AU  - G. Richard
AU  - C. Noll
AU  - O. Sarrhini
AU  - W. Mampuya
AU  - S. Phoenix
AU  - L. Bouffard
AU  - B. Guerin
AU  - E. Turcotte
AU  - F. Rutters
AU  - P. Raina
AU  - J.-P. Despres
AU  - J. Hoeks
AU  - P. Schrauwen
AU  - A. C. Carpentier
AU  - D. P. Blondin
PY  - 2026
DA  - 2026/10/23
PB  - medRxiv
DO  - 10.64898/2026.10.23.26365753
UR  - https://www.medrxiv.org/content/10.64898/2026.10.23.26365753v1
AB  - 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.  HighlightsO_LIAfter a meal, net palmitate uptake fall in all tissues but extraction rises in most C_LIO_LIAfter a meal, the liver directs palmitate toward esterification and the heart toward oxidation C_LIO_LIPlasma NEFA level underestimate lean tissue NEFA exposure after a meal in prediabetes C_LI
ER  -

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