Lipolysis-derived linoleic acid drives beige fat progenitor cell proliferation

Ichitaro Abe; Yasuo Oguri; Anthony R P Verkerke; Lauar B Monteiro; Carly M Knuth; Christopher Auger; Yunping Qiu; Gregory P Westcott; Saverio Cinti; Kosaku Shinoda; Marc G Jeschke; Shingo Kajimura

doi:10.1016/j.devcel.2022.11.007

Lipolysis-derived linoleic acid drives beige fat progenitor cell proliferation

Dev Cell. 2022 Dec 5;57(23):2623-2637.e8. doi: 10.1016/j.devcel.2022.11.007.

Authors

Affiliations

¹ Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
² Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
³ Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
⁴ Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
⁵ Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
⁶ Center of Obesity, Marche Polytechnic University, Ancona, Italy.
⁷ Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Division of Endocrinology & Diabetes, Albert Einstein College of Medicine, Bronx, NY, USA; Albert Einstein College of Medicine, Fleischer Institute for Diabetes and Metabolism, Bronx, NY, USA.
⁸ Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada; Ross Tilley Burn Centre, Sunnybrook Hospital, Toronto, ON, Canada; Department of Surgery, Division of Plastic Surgery, and Department of Immunology, University of Toronto, Toronto, ON, Canada.
⁹ Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: skajimur@bidmc.harvard.edu.

Abstract

De novo beige adipocyte biogenesis involves the proliferation of progenitor cells in white adipose tissue (WAT); however, what regulates this process remains unclear. Here, we report that in mouse models but also in human tissues, WAT lipolysis-derived linoleic acid triggers beige progenitor cell proliferation following cold acclimation, β3-adrenoceptor activation, and burn injury. A subset of adipocyte progenitors, as marked by cell surface markers PDGFRα or Sca1 and CD81, harbored cristae-rich mitochondria and actively imported linoleic acid via a fatty acid transporter CD36. Linoleic acid not only was oxidized as fuel in the mitochondria but also was utilized for the synthesis of arachidonic acid-derived signaling entities such as prostaglandin D₂. Oral supplementation of linoleic acid was sufficient to stimulate beige progenitor cell proliferation, even under thermoneutral conditions, in a CD36-dependent manner. Together, this study provides mechanistic insights into how diverse pathophysiological stimuli, such as cold and burn injury, promote de novo beige fat biogenesis.

Keywords: adipose tissue development; beige adipocytes; bioenergetics; brown adipose tissue; lipolysis; metabolic disease; progenitor cells; white adipose tissue.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue, Beige*
Animals
Cell Proliferation
Humans
Linoleic Acid* / pharmacology
Mice

Substances

Linoleic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding