Adrenergically stimulated blood flow in brown adipose tissue is not dependent on thermogenesis.
Brown adipose tissue (BAT) thermogenesis relies on blood flow to be supplied with nutrients and oxygen and for the distribution of the generated heat to the rest of the body. Therefore, it is fundamental to understand the mechanisms by which blood flow is regulated and its relation to thermogenesis. Here, we present high-resolution laser-Doppler imaging (HR-LDR) as a novel method for noninvasive in vivo measurement of BAT blood flow in mice. Using HR-LDR, we found that norepinephrine stimulation increases BAT blood flow in a dose-dependent manner and that this response is profoundly modulated by environmental temperature acclimation. Surprisingly, we found that mice lacking uncoupling protein 1 (UCP1) have fully preserved BAT blood flow response to norepinephrine despite failing to perform thermogenesis. BAT blood flow was not directly correlated to systemic glycemia, but glucose injections could transiently increase tissue perfusion. Inguinal white adipose tissue, also known as a brite/beige adipose tissue, was also sensitive to cold acclimation and similarly increased blood flow in response to norepinephrine. In conclusion, using a novel noninvasive method to detect BAT perfusion, we demonstrate that adrenergically stimulated BAT blood flow is qualitatively and quantitatively fully independent of thermogenesis, and therefore, it is not a reliable parameter for the estimation of BAT activation and heat generation.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; and.
Gustavo
G
Abreu-Vieira
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Carolina E
CE
Hagberg
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Kirsty L
KL
Spalding
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; and.
Barbara
B
Cannon
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; and jan@metabol.su.se.
Jan
J
Nedergaard
D000064:Acclimatization / Q000187:drug effects; D002001:Adipose Tissue, Brown / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects*; D022722:Thermogenesis / Q000502:physiology*
D018663:Adrenergic Agents; D009638:Norepinephrine
blood flow; brown adipose tissue; high-resolution laser-Doppler imaging; thermogenesis; uncoupling protein 1.