ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure

• Published in: eLife 2015-10, Vol.4
• Main Authors: Dijk, Wieneke, Heine, Markus, Vergnes, Laurent, Boon, Mariëtte R, Schaart, Gert, Hesselink, Matthijs K C, Reue, Karen, van Marken Lichtenbelt, Wouter D, Olivecrona, Gunilla, Rensen, Patrick C N, Heeren, Joerg, Kersten, Sander
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose tissue (brown); Adipose Tissue, Brown - chemistry; Angiopoietin; angiopoietin-like 4; Angiopoietin-like 4 Protein; Angiopoietins - metabolism; Animal biology; Animals; Biochemistry, Molecular Biology; Biology; Body fat; Brown adipose tissue; Cellular Biology; Chair Nutrition Metabolism and Genomics; Cold; Cold Temperature; energy metabolism; Energy resources; Fatty acids; Fatty Acids - metabolism; Growth factors; HNE Nutrition, Metabolism and Genomics; HNE Voeding, Metabolisme en Genomics; Human Biology and Medicine; Life Sciences; Lipase; Lipids; Lipoprotein lipase; Lipoproteins; Metabolism; Mice; Molecular weight; Non-shivering; Nutrition; Nutrition, Metabolism and Genomics; Physiological aspects; Plasma - chemistry; Proteins; Rodents; Thermal properties; Thermogenesis; triglyceride-rich lipoproteins; VLAG; Voeding, Metabolisme en Genomica; white adipose tissue
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.08428

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.