Brown Adipose Tissue Blood Flow and Mass in Obesity: A Contrast Ultrasound Study in Mice

Abstract

Background When activated by the sympathetic nervous system, brown adipose tissue (BAT) increases energy expenditure to produce heat. Augmenting BAT mass or increasing BAT activation could potentially be used to decrease obesity. Noninvasive methods to detect and monitor BAT mass are needed. Contrast ultrasound can estimate BAT blood flow and is able to measure the perfused volume of an organ and thus its mass. The objective of this study was to evaluate whether contrast ultrasound could characterize BAT mass in two mouse models of obesity: wild-type mice fed a high-fat diet and mutant db/db mice. Methods Contrast ultrasound of BAT (Definity 2 μL/min; 14-MHz linear probe) was performed before and after stimulation of BAT with norepinephrine (NE). BAT replenishment curves were obtained, and blood flow was estimated by the product of the curve’s plateau and slope. Additionally, consecutive two-dimensional images of perfused BAT were acquired at 1-mm intervals after stimulation with NE and used to assess BAT volume and mass. Results BAT blood flow increased after NE infusion in all mice studied. Blood flow response to NE was similar in wild-type mice fed either a low-fat diet or a high-fat diet. BAT blood flow was lower in db/db mice than in wild-type mice (P = .02). Contrast ultrasound–derived BAT mass was correlated with BAT mass obtained at necropsy (R2 = 0.83, P < .001). BAT mass was higher in mice fed a high-fat diet than in those fed a low-fat diet. Conclusions Contrast ultrasound can be used to estimate BAT mass in mice when BAT vascularization is not significantly impaired. This noninvasive technique may potentially allow the serial evaluation of therapies designed to augment BAT mass.

Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI

“…The enhancement is very localized and large enough to enable the fast acquisition of background-free maps of this tissue, with relatively low polarization levels (8-10%) and without the use of more expensive 129 Xe-enriched gas. Interestingly, xenon signal enhancement is observed not only in lean but also in the obese mouse phenotype in which capillary density, tissue blood flow, and thermogenic activity are all known to be reduced (21). This is probably because the lipid-rich BAT of obese mice represents a better host for lipophilic xenon, thereby compensating for the reduction in blood flow and capillary density.…”

“…BAT thermogenesis is still detected indirectly, either through surface temperature measurements (infrared thermography) that are inherently affected by local changes in tissue blood flow (20) or by measurements of tissue blood flow (ultrasound), which is only partially coupled to BAT thermogenic activity (11) and which exhibits the same insensitivity to the less vascularized lipidrich BAT of obese phenotypes (21).…”

Imaging of Brown Adipose Tissue: State of the Art

“…This is supported by the observation that a norepinephrineinduced increase in BAT perfusion was blunted in mice lacking UCP1, which also fails to induce oxygen consumption and thermogenesis in response to norepinephrine (94). In follow-up work, the same group demonstrated that total BAT mass could also be derived by using steady-state imaging during continuous norepinephrine and microbubble administration (95). Contrast-enhanced US-derived BAT mass correlated well with mass at necropsy, and the technique demonstrated reasonable intra-and interobserver variability.…”

Insights into Brown Adipose Tissue Physiology as Revealed by Imaging Studies

“…87 In a different study, infusion of the same dose of norepinephrine resulted in a similar increase in BAT blood flow (15-fold20-increase) in wild type mice fed a low fat diet or high fat diet for 2 months, with a higher increase in blood flow in the low fat diet mice. 88 In db/db (obese diabetic leptin receptor-deficient) mice, baseline blood flow to BAT was significantly lower than wild type and norepinephrine increased BAT blood flow to a lesser extent (about fold10-increase). 88 Additionally, these authors were able to estimate BAT mass using contrast ultrasound in the wild type mice, and the estimates correlated well with BAT mass measured at necropsy (r 2 D 0.83, P<0 .001).…”

“…88 In db/db (obese diabetic leptin receptor-deficient) mice, baseline blood flow to BAT was significantly lower than wild type and norepinephrine increased BAT blood flow to a lesser extent (about fold10-increase). 88 Additionally, these authors were able to estimate BAT mass using contrast ultrasound in the wild type mice, and the estimates correlated well with BAT mass measured at necropsy (r 2 D 0.83, P<0 .001).…”