@article{6be11a7523d64c1bb3e5bc4ed6e7b8bf,
title = "Lipolysis-derived linoleic acid drives beige fat progenitor cell proliferation",
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",
author = "Ichitaro Abe and Yasuo Oguri and Verkerke, {Anthony R.P.} and Monteiro, {Lauar B.} and Knuth, {Carly M.} and Christopher Auger and Yunping Qiu and Westcott, {Gregory P.} and Saverio Cinti and Kosaku Shinoda and Jeschke, {Marc G.} and Shingo Kajimura",
note = "Funding Information: We are grateful to Dr. B. Kahn at BIDMC for providing Pnpla2 flox/flox mice; Drs. E.D. Rosen, A. Gulko, and L. Lumkong at BIDMC for their help with human tissue sample management; Dr. A. Banks at BIDMC for their support in metabolic cage studies; and Dr. O. Quehenberger at the University of California, San Diego for discussions on lipidomics. We thank J. Wong, T. Yamamuro, Q. Wang, Z.H. Taxin, D. Kato, and S. Oikawa in the Kajimura lab for their technical help. This work was supported by the NIH (DP1DK126160 and RO1DK125281) and the Howard Hughes Medical Institute to S.K. and R01GM133961 to M.G.J. I.A. is supported by the Japan Heart Foundation Research Grant and by the Uehara Memorial Foundation. A.R.P.V. is supported by NIH T32DK007516. I.A. and Y.O. designed and carried out the experiments and analyzed the data. A.R.P.V. performed fatty acid and lipidomics experiments. L.B.M. C.M.K. and C.A. performed burn injury model animal experiments under the supervision of M.G.J. Y.Q. performed the eicosanoids quantification. G.P.W. carried out human sample management and analysis. K.S. performed RNA-seq analyses and bioinformatics. S.C. assisted EM analyses and interpreted the data. S.K. conceived the project and directed the overall research. I.A. and S.K. wrote the paper with input from all of the authors. The authors declare no competing interests. Funding Information: We are grateful to Dr. B. Kahn at BIDMC for providing Pnpla2 flox/flox mice; Drs. E.D. Rosen, A. Gulko, and L. Lumkong at BIDMC for their help with human tissue sample management; Dr. A. Banks at BIDMC for their support in metabolic cage studies; and Dr. O. Quehenberger at the University of California, San Diego for discussions on lipidomics. We thank J. Wong, T. Yamamuro, Q. Wang, Z.H. Taxin, D. Kato, and S. Oikawa in the Kajimura lab for their technical help. This work was supported by the NIH ( DP1DK126160 and RO1DK125281 ) and the Howard Hughes Medical Institute to S.K., and R01GM133961 to M.G.J. I.A. is supported by the Japan Heart Foundation Research Grant and by the Uehara Memorial Foundation . A.R.P.V. is supported by NIH T32DK007516 . Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = dec,
day = "5",
doi = "10.1016/j.devcel.2022.11.007",
language = "English (US)",
volume = "57",
pages = "2623--2637.e8",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "23",
}