Lipid Droplets in Brown Adipose Tissue Are Dispensable for Cold-Induced Thermogenesis
Chandramohan Chitraju,
Alexander W. Fischer,
Robert V. Farese, Jr.,
Tobias C. Walther
Affiliations
Chandramohan Chitraju
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Alexander W. Fischer
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Robert V. Farese, Jr.
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Corresponding author
Tobias C. Walther
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA; Corresponding author
Summary: Brown adipocytes store metabolic energy as triglycerides (TGs) in lipid droplets (LDs). Fatty acids released from brown adipocyte LDs by lipolysis are thought to activate and fuel UCP1-mediated thermogenesis. Here, we test this hypothesis by preventing fatty acid storage in murine brown adipocytes through brown adipose tissue (BAT)-specific deletions of the TG synthesis enzymes DGAT1 and DGAT2 (BA-DGAT KO). Despite the absence of TGs in brown adipocytes, BAT is functional, and BA-DGAT-KO mice maintain euthermia during acute or chronic cold exposure. As apparent adaptations to the lack of TG, brown adipocytes of BA-DGAT-KO mice appear to use circulating glucose and fatty acids, and stored glycogen, to fuel thermogenesis. Moreover, BA-DGAT-KO mice are resistant to diet-induced glucose intolerance, likely because of increased glucose disposal by BAT. We conclude that TGs in BAT are dispensable for its contribution to cold-induced thermogenesis, at least when other fuel sources are available.
