Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors
Rohan Varshney,
Snehasis Das,
G. Devon Trahan,
Jacob W. Farriester,
Gregory P. Mullen,
Gertrude Kyere-Davies,
David M. Presby,
Julie A. Houck,
Patricia G. Webb,
Monika Dzieciatkowska,
Kenneth L. Jones,
Matthew S. Rodeheffer,
Jacob E. Friedman,
Paul S. MacLean,
Michael C. Rudolph
Affiliations
Rohan Varshney
Harold Hamm Diabetes Center and Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Snehasis Das
Harold Hamm Diabetes Center and Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
G. Devon Trahan
Department of Pediatrics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
Jacob W. Farriester
Harold Hamm Diabetes Center and Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Gregory P. Mullen
Harold Hamm Diabetes Center and Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Gertrude Kyere-Davies
Harold Hamm Diabetes Center and Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
David M. Presby
Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO, USA
Julie A. Houck
Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO, USA
Patricia G. Webb
Department of Reproductive Science, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO, USA
Monika Dzieciatkowska
Department of Biochemistry & Molecular Genetics, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO, USA
Kenneth L. Jones
Department of Cell Biology and Harold Hamm Diabetes Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Matthew S. Rodeheffer
Department of Molecular, Cellular and Developmental Biology, Department of Comparative Medicine, Yale University, New Haven, CT, USA
Jacob E. Friedman
Harold Hamm Diabetes Center and Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Paul S. MacLean
Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO, USA
Michael C. Rudolph
Harold Hamm Diabetes Center and Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Corresponding author
Summary: Establishing metabolic programming begins during fetal and postnatal development, and early-life lipid exposures play a critical role during neonatal adipogenesis. We define how neonatal consumption of a low omega-6 to −3 fatty acid ratio (n6/n3 FA ratio) establishes FA oxidation in adipocyte precursor cells (APCs) before they become adipocytes. In vivo, APCs isolated from mouse pups exposed to the low n6/n3 FA ratio had superior FA oxidation capacity, elevated beige adipocyte mRNAs Ppargc1α, Ucp2, and Runx1, and increased nuclear receptor NR2F2 protein. In vitro, APC treatment with NR2F2 ligand-induced beige adipocyte mRNAs and increased mitochondrial potential but not mass. Single-cell RNA-sequencing analysis revealed low n6/n3 FA ratio yielded more mitochondrial-high APCs and linked APC NR2F2 levels with beige adipocyte signatures and FA oxidation. Establishing beige adipogenesis is of clinical relevance, because fat depots with energetically active, smaller, and more numerous adipocytes improve metabolism and delay metabolic dysfunction.
