@article{46c90401bff54de0b01fe9567728fec7,
title = "Mitochondrial metabolism is a key regulator of the fibro-inflammatory and adipogenic stromal subpopulations in white adipose tissue",
abstract = "The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their behaviors in response to stimuli, such as overfeeding, however, are unclear. Here, we show that the developmental fates and functional properties of adipose platelet-derived growth factor receptor beta (PDGFRβ)+ progenitor subpopulations are tightly regulated by mitochondrial metabolism. Reducing the mitochondrial β-oxidative capacity of PDGFRβ+ cells via inducible expression of MitoNEET drives a pro-inflammatory phenotype in adipose progenitors and alters lineage commitment. Furthermore, disrupting mitochondrial function in PDGFRβ+ cells rapidly induces alterations in immune cell composition in lean mice and impacts expansion of adipose tissue in diet-induced obesity. The adverse effects on adipose tissue remodeling can be reversed by restoring mitochondrial activity in progenitors, suggesting therapeutic potential for targeting energy metabolism in these cells.",
keywords = "adipocyte, adipogenesis, inflammation, metabolism, mitochondria, stem cells",
author = "Nolwenn Joffin and Paschoal, {Vivian A.} and Gliniak, {Christy M.} and Clair Crewe and Abdallah Elnwasany and Szweda, {Luke I.} and Qianbin Zhang and Chelsea Hepler and Kusminski, {Christine M.} and Ruth Gordillo and Oh, {Da Young} and Gupta, {Rana K.} and Scherer, {Philipp E.}",
note = "Funding Information: We thank the following UT Southwestern Core Units: Histology Core for assistance in embedding and processing of tissue samples and the Metabolic Phenotyping Core for hepatic lipid content measurements. We also thank The Flow Cytometry Core at the Children{\textquoteright}s Medical Center Research Institute at UT Southwestern. We would like to acknowledge the help of Dr. Jan-Bernd Funcke for the graphical abstract. This study was supported by US National Institutes of Health (NIH) grants R01-DK55758 , P01-DK088761 , R01-DK099110 , and P01-AG051459 (P.E.S.); F32-DK113704 (C.C.); F31-DK113696 (C.H.); R01-DK104789 and R01 DK119163 (R.K.G.); and RC2-DK118620 (P.E.S. and R.K.G.). N.J. was supported by a post-doctoral fellowship from the Lipedema Foundation (LFA no. 18 ). (L.I.S.) Foundation Leducq ( 17CVD04 ) and NIH ( R01-HL138983 ) Funding Information: We thank the following UT Southwestern Core Units: Histology Core for assistance in embedding and processing of tissue samples and the Metabolic Phenotyping Core for hepatic lipid content measurements. We also thank The Flow Cytometry Core at the Children's Medical Center Research Institute at UT Southwestern. We would like to acknowledge the help of Dr. Jan-Bernd Funcke for the graphical abstract. This study was supported by US National Institutes of Health (NIH) grants R01-DK55758, P01-DK088761, R01-DK099110, and P01-AG051459 (P.E.S.); F32-DK113704 (C.C.); F31-DK113696 (C.H.); R01-DK104789 and R01 DK119163 (R.K.G.); and RC2-DK118620 (P.E.S. and R.K.G.). N.J. was supported by a post-doctoral fellowship from the Lipedema Foundation (LFA no. 18). (L.I.S.) Foundation Leducq (17CVD04) and NIH (R01-HL138983), N.J. conceptualized the project; designed experiments; analyzed and interpreted data; conducted experiments, with the exception of those listed below; and wrote the manuscript. V.A.P. assisted with flow cytometry, mouse experiments, and sample processing. C.M.G. performed mtDNA experiments. C.M.G. and C.C. helped with mouse experiments and editing manuscript. A.E. and L.I.S. performed LDH experiments. Q.Z. and C.H. assisted in flow cytometry. C.M.K. assisted with mouse experiments and conceptualizing the experiments. R.G. performed hepatic triglyceride measurements. D.Y.O. provided guidance. P.E.S. and R.K.G. were involved in conceptualizing the approach, experimental design, and the writing of the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = apr,
day = "1",
doi = "10.1016/j.stem.2021.01.002",
language = "English (US)",
volume = "28",
pages = "702--717.e8",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "4",
}