title: ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure.
abstract: Brown adipose tissue (BAT) activation via cold exposure is increasingly scrutinized as a potential approach to ameliorate cardio-metabolic risk. Transition to cold temperatures requires changes in the partitioning of energy substrates, re-routing fatty acids to BAT to fuel non-shivering thermogenesis. However, the mechanisms behind the redistribution of energy substrates to BAT remain largely unknown. Angiopoietin-like 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT. Here, we demonstrate that ANGPTL4 is part of a shuttling mechanism that directs fatty acids derived from circulating triglyceride-rich lipoproteins to BAT during cold. Specifically, we show that cold markedly down-regulates ANGPTL4 in BAT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived fatty acids. In contrast, cold up-regulates ANGPTL4 in WAT, abolishing a cold-induced increase in LPL activity. Together, our data indicate that ANGPTL4 is an important regulator of plasma lipid partitioning during sustained cold.
authors.affiliation: Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Wieneke
authors.initials: W
authors.lastname: Dijk
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Heine
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.|Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vergnes
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden Univeristy Medical Center, Leiden, The Netherlands.
authors.forename: Mariëtte R
authors.initials: MR
authors.lastname: Boon
authors.affiliation: Department of Human Movement Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.affiliation: Department of Human Movement Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Matthijs K C
authors.initials: MK
authors.lastname: Hesselink
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.|Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
authors.affiliation: Department of Human Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Wouter D
authors.initials: WD
authors.lastname: van Marken Lichtenbelt
authors.affiliation: Department of Medical Biosciences/Physiological Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden Univeristy Medical Center, Leiden, The Netherlands.
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Heeren
authors.affiliation: Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
mesh_terms: D002001:Adipose Tissue, Brown / Q000737:chemistry*; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D005227:Fatty Acids / Q000378:metabolism*; D051379:Mice; D010949:Plasma / Q000737:chemistry
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D005227:Fatty Acids
keywords: angiopoietin-like 4; brown adipose tissue; energy metabolism; human biology; lipoprotein lipase; medicine; mouse; triglyceride-rich lipoproteins; white adipose tissue