American Diabetes Association
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Total postprandial hepatic non-esterified and dietary fatty acid uptake is increased and insufficiently curbed by adipose tissue fatty acid trapping in prediabetes with overweight

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posted on 2022-06-24, 09:10 authored by Run Zhou Ye, Émilie Montastier, Christophe Noll, Frédérique Frisch, Mélanie Fortin, Lucie Bouffard, Serge Phoenix, Brigitte Guérin, Éric E. Turcotte, André C. Carpentier

Excessive lean tissue uptake of fatty acids (FA) is important in the development of insulin resistance and may be caused by impaired dietary FA (DFA) storage and/or increased non-esterified FA (NEFA) flux from adipose tissue intracellular lipolysis. Cardiac and hepatic total postprandial FA uptake of NEFA+DFA has, however, never been reported in prediabetes with overweight. Twenty individuals with impaired glucose tolerance (IGT) and 19 participants with normal glucose tolerance (NGT) and normal fasting glucose underwent postprandial studies with whole-body positron emission tomography/computed tomography (PET/CT) with oral [18F]-fluoro-thia-heptadecanoic acid and dynamic PET/CT with intravenous [11C]-palmitate. Hepatic (97[range 36-215]mmol/6h vs. 68[23-132]mmol/6h, P=0.03), but not cardiac (11[range 4-24]mmol/6h vs. 8[3-20]mmol/6h, P=0.09) uptake of most sources of postprandial FA (NEFA+DFA uptake) integrated over 6 hours was higher in IGT vs. NGT. DFA accounted for lower fractions of total cardiac (21[5-47]% vs. 25[9-39]%, P=0.08) and hepatic (19[6-52]% vs. 28[14-50]%, P=0.04) uptake in IGT vs. NGT. Increased adipose tissue DFA trapping predicted lower hepatic DFA uptake, and was associated with higher total cardiac fatty acid uptake. Hence, enhanced adipose tissue DFA trapping in the face of increased postprandial NEFA flux is insufficient to fully curb increased postprandial lean organ FA uptake in prediabetes with overweight (; NCT02808182). 


This work was supported by a grant from the Canadian Institutes of Health Research (CIHR Operating Grant MOP53094). A. C. Carpentier holds the Canada Research Chair in Molecular Imaging of Diabetes.