Dietary oleic acid drives obesogenic adipogenesis via modulation of LXRα signaling
Allison Wing,
Elise Jeffery,
Christopher D. Church,
Jennifer Goodell,
Rocío del M. Saavedra-Peña,
Moumita Saha,
Brandon Holtrup,
Maud Voisin,
N. Sima Alavi,
Mariana Floody,
Zenan Wang,
Thomas E. Zapadka,
Michael J. Garabedian,
Rohan Varshney,
Michael C. Rudolph,
Matthew S. Rodeheffer
Affiliations
Allison Wing
Department of Molecular, Cell, and Developmental Biology, Yale University, 219 Prospect St., New Haven, CT 06520, USA
Elise Jeffery
Department of Cell Biology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520, USA
Christopher D. Church
Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar St., New Haven, CT 06520, USA
Jennifer Goodell
Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar St., New Haven, CT 06520, USA
Rocío del M. Saavedra-Peña
Department of Molecular, Cell, and Developmental Biology, Yale University, 219 Prospect St., New Haven, CT 06520, USA
Moumita Saha
Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar St., New Haven, CT 06520, USA
Brandon Holtrup
Department of Molecular, Cell, and Developmental Biology, Yale University, 219 Prospect St., New Haven, CT 06520, USA
Maud Voisin
Department of Microbiology, NYU School of Medicine, New York, NY 10016, USA
N. Sima Alavi
Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar St., New Haven, CT 06520, USA
Mariana Floody
Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar St., New Haven, CT 06520, USA
Zenan Wang
Department of Molecular, Cell, and Developmental Biology, Yale University, 219 Prospect St., New Haven, CT 06520, USA
Thomas E. Zapadka
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA
Michael J. Garabedian
Department of Microbiology, NYU School of Medicine, New York, NY 10016, USA; Department of Medicine, NYU School of Medicine, New York, NY 10016, USA
Rohan Varshney
Department of Biochemistry and Physiology and Harold Hamm Diabetes Center, Oklahoma University Health Sciences, Oklahoma City, OK 73104, USA
Michael C. Rudolph
Department of Biochemistry and Physiology and Harold Hamm Diabetes Center, Oklahoma University Health Sciences, Oklahoma City, OK 73104, USA; Corresponding author
Matthew S. Rodeheffer
Department of Molecular, Cell, and Developmental Biology, Yale University, 219 Prospect St., New Haven, CT 06520, USA; Department of Cell Biology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University School of Medicine, 10 Amistad St., New Haven, CT 06520, USA; Yale Center of Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA; Corresponding author
Summary: Dietary fat composition has changed substantially during the obesity epidemic. As adipocyte hyperplasia is a major mechanism of adipose expansion, we aim to ascertain how dietary fats affect adipogenesis during obesity. We employ an unbiased dietary screen to identify oleic acid (OA) as the only dietary fatty acid that induces obesogenic hyperplasia at physiologic levels and show that plasma monounsaturated fatty acids (MUFAs), which are mostly OA, are associated with human obesity. OA stimulates adipogenesis in mouse and human adipocyte precursor cells (APCs) by increasing AKT2 signaling, a hallmark of obesogenic hyperplasia, and reducing LXR activity. High OA consumption decreases LXRα Ser196 phosphorylation in APCs, while blocking LXRα phosphorylation results in APC hyperproliferation. As OA is increasingly being incorporated into dietary fats due to purported health benefits, our finding that OA is a unique physiologic regulator of adipose biology underscores the importance of understanding how high OA consumption affects metabolic health.
