Adipocyte hypertrophy associates with in vivo postprandial fatty acid metabolism and adipose single-cell transcriptional dynamics
Run Zhou Ye,
Emilie Montastier,
Frédérique Frisch,
Christophe Noll,
Hugues Allard-Chamard,
Nicolas Gévry,
André Tchernof,
André C. Carpentier
Affiliations
Run Zhou Ye
Division of Endocrinology, Department of Medicine, Centre de recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Emilie Montastier
Division of Endocrinology, Department of Medicine, Centre de recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Frédérique Frisch
Division of Endocrinology, Department of Medicine, Centre de recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Christophe Noll
Division of Endocrinology, Department of Medicine, Centre de recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Hugues Allard-Chamard
Division of Endocrinology, Department of Medicine, Centre de recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Nicolas Gévry
Department of Biology, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
André Tchernof
Québec Heart and Lung Research Institute, Laval University, Québec, QC G1V 4G5, Canada
André C. Carpentier
Division of Endocrinology, Department of Medicine, Centre de recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; Department of Nuclear Medicine and Radiobiology, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; Corresponding author
Summary: Adipocyte hypertrophy is associated with metabolic complications independent of obesity. We aimed to determine: 1) the association between adipocyte size and postprandial fatty acid metabolism; 2) the potential mechanisms driving the obesity-independent, hypertrophy-associated dysmetabolism in vivo and at a single-cell resolution. Tracers with positron emission tomography were used to measure fatty acid metabolism in 40 men and women with normal or impaired glucose tolerance (NCT02808182), and single nuclei RNA-sequencing (snRNA-seq) to determine transcriptional dynamics of subcutaneous adipose tissue (AT) between individuals with AT hypertrophy vs. hyperplasia matched for sex, ethnicity, glucose-tolerance status, BMI, total and percent body fat, and waist circumference. Adipocyte size was associated with high postprandial total cardiac fatty acid uptake and higher visceral AT dietary fatty acid uptake, but lower lean tissue dietary fatty acid uptake. We found major shifts in cell transcriptomal dynamics with AT hypertrophy that were consistent with in vivo metabolic changes.
