Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation.

Autor:	Fischer AW; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Jaeckstein MY; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Gottschling K; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Heine M; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sass F; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Mangels N; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schlein C; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Worthmann A; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Bruns OT; Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany., Yuan Y; Department of Chemistry, Brown University, Providence, RI, USA., Zhu H; Department of Chemistry, Brown University, Providence, RI, USA., Chen O; Department of Chemistry, Brown University, Providence, RI, USA., Ittrich H; Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Nilsson SK; Department of Medical Biosciences, Umeå University, Umeå, Sweden., Stefanicka P; Department of Otorhinolaryngology - Head and Neck Surgery, Comenius University, Bratislava, Slovakia., Ukropec J; Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, Bratislava, Slovakia., Balaz M; Institute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland., Dong H; Institute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland., Sun W; Institute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland., Reimer R; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany., Scheja L; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Heeren J; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: heeren@uke.de.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2021 Mar 02; Vol. 33 (3), pp. 547-564.e7. Date of Electronic Publication: 2020 Dec 22.
DOI:	10.1016/j.cmet.2020.12.001
Abstrakt:	In response to cold exposure, thermogenic adipocytes internalize large amounts of fatty acids after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TRL) in the capillary lumen of brown adipose tissue (BAT) and white adipose tissue (WAT). Here, we show that in cold-exposed mice, vascular endothelial cells in adipose tissues endocytose substantial amounts of entire TRL particles. These lipoproteins subsequently follow the endosomal-lysosomal pathway, where they undergo lysosomal acid lipase (LAL)-mediated processing. Endothelial cell-specific LAL deficiency results in impaired thermogenic capacity as a consequence of reduced recruitment of brown and brite/beige adipocytes. Mechanistically, TRL processing by LAL induces proliferation of endothelial cells and adipocyte precursors via beta-oxidation-dependent production of reactive oxygen species, which in turn stimulates hypoxia-inducible factor-1α-dependent proliferative responses. In conclusion, this study demonstrates a physiological role for TRL particle uptake into BAT and WAT and establishes endothelial lipoprotein processing as an important determinant of adipose tissue remodeling during thermogenic adaptation. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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