Adrenergically stimulated blood flow in brown adipose tissue is not dependent on thermogenesis

Abstract

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.

Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1–Deficient Mice

“…In human PET imaging studies, brown adipose tissue (BAT) 18 F-FDG uptake has been shown to be markedly increased by controlled cold exposure (1,2) and agonism of b3 adrenergic receptors (3), correlating positively with changes in energy expenditure (1,3). Similar findings have been made in small-animal PET imaging studies performed on mice (4,5).…”

“…Both WT and UCP1 KO mice showed an increased mean SUV for 18 F-FDG in BAT in response to CL 316, 243 treatment relative to vehicle treatment (P , 0.0001) (Fig. 3B), with no significant effect of genotype found (F 1, 14 5 0.17, P 5 0.68).…”

“…Additional techniques that measure BAT thermogenesis apart from 18 F-FDG PET imaging and blood flow measurements (18) are required in model systems in which UCP1 is expected not to be functional. Because UCP1 deficiency is not the standard physiologic scenario in humans, caution is, however, warranted when translating our findings.…”

“…It is widely assumed that BAT 18 F-FDG uptake provides an indirect quantitative measure of thermogenesis. We therefore sought to formally test this basic assumption by performing 18 F-FDG PET/MRI experiments on UCP1-deficient mice that exhibit defective BAT thermogenesis and uncoupled respiration in response to the selective b3 adrenergic receptor agonist CL 316, 243 (7,8).…”

Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults

“…These observations suggest that an important function of BAT innervation might be the redistribution of core heat to critical regions in the supraclavicular and spinal regions. In this regard, norepinephrine infusion was recently shown to dramatically increase blood flow to murine BAT in the absence of UCP1-mediated thermogenesis (42).…”