Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation

Mirbolooki, Mohammadreza; Constantinescu, Cristian; Pan, Min; Mukherjee, Jogeshwar

doi:10.1186/2191-219x-1-30

Cited by 74 publications

(88 citation statements)

References 26 publications

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“…The results of this study show that 18 F-FDG uptake of interscapular BAT is prominently increased by a single challenge with CL316,243, which is consistent with acute metabolic responses previously ob- served in mice (17,18) and humans (5,6). Interscapular BAT thus served as a positive control in our study to investigate the ability of 18 F-FDG imaging to monitor beige cell recruitment into WAT.…”

Section: Discussionsupporting

confidence: 61%

“…In identifying the mediators for increased 18 F-FDG uptake by b3AR stimulation, BAT displayed high expression of both GLUT4 and hexokinase-II regardless of treatment (Fig. 3).…”

Section: Glut4 and Hexokinase-ii Expression In Inguinal Watmentioning

confidence: 99%

“…Uptake was greatest for mesenteric WAT, followed by retroperitoneal WAT, and was lowest for epididymal WAT (15.3 6 2.4, 12.3 6 0.7, and 0.7 6 0.3 %ID/g, respectively, at day 7). 18 F-FDG uptake of BAT and WAT are compared side by side in supplemental Figure 1B.…”

Section: Acute Stimulation Of Interscapular Bat 18 F-fdg Uptakementioning

confidence: 99%

“…Circular regions of interest were placed in the left lung as background activity. From each region of interest, mean standardized uptake values and targetto-background ratios were measured as indices of 18 …”

Section: Animal Preparation and Cl316243 Treatmentmentioning

confidence: 99%

“…However, such studies to date have been limited mostly to acute BAT activation. Although b3AR stimulation has recently been shown to increase 18 F-FDG uptake in WAT of rodents (15,16), whether the level of 18 F-FDG uptake has sufficient accuracy to faithfully represent the magnitude of WAT browning has not been properly investigated. If 18 F-FDG can be shown to be a reliable biomarker, PET/CT imaging may help foster the in vivo translation of recent molecular discoveries related to WAT browning and may provide insight on how obesity can be treated by modifying WAT metabolism.…”

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confidence: 99%

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¹⁸F-FDG PET/CT Monitoring of β3 Agonist–Stimulated Brown Adipocyte Recruitment in White Adipose Tissue

et al. 2014

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There is rising interest in recruitment of brown adipocytes into white adipose tissue (WAT) as a means to augment energy expenditure for weight reduction. We thus investigated the potential of 18 F-FDG uptake as an imaging biomarker that can monitor the process of WAT browning. Methods: C57BL/6 mice were treated daily with the β3 agonist CL316,243 (5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl] amino]propyl]-1,3-benzodioxole-2,2-dicarboxylic acid disodium salt), whereas controls received saline. 18 F-FDG small-animal PET/CT was serially performed at 1 h after CL316,243 injection. After sacrifice, interscapular brown adipose tissue (BAT) and WAT depots were extracted, weighed, and measured for 18 F-FDG uptake. Tissues underwent immunostaining, and UCP1 content was quantified by Western blotting. Results: PET/CT showed low 18 F-FDG uptake in both BAT and inguinal WAT at baseline. BAT uptake was substantially increased by a single stimulation with CL316,243. Uptake in inguinal WAT was only modestly elevated by the first stimulation uptake but gradually increased to BAT level by prolonged stimulation. Ex vivo measurements recapitulated the PET findings, and measured 18 F-FDG uptake in other WAT depots was similar to inguinal WAT. WAT browning by prolonged stimulation was confirmed by a substantial increase in uncoupling protein 1 (UCP1), cytochrome-c oxidase 4 (COX4), and PR domain containing 16 (PRDM16) staining as markers of brown adipocytes. UCP1 content, which served as a measure for extent of browning, was low in baseline inguinal WAT but linearly increased over 10 d of CL316,243 injection. Finally, image-based and ex vivo-measured 18 F-FDG uptake in inguinal WAT correlated well with UCP1 content. Conclusion: 18 F-FDG PET/CT has the capacity to monitor brown adipocyte recruitment into WAT depots in vivo and may thus be useful for screening the efficacy of strategies to promote WAT browning. Subcut aneous and visceral white adipose tissue (WAT) contributes to obesity by storing excess energy as intracellular lipid (1,2). By contrast, brown adipose tissue (BAT) can have a negative influence on weight gain by dissipating energy as heat (3,4). This thermoregulatory response is mediated through norepinephrineactivated b3 adrenergic receptor (b3AR) signaling. The exciting recent revelation that functional BAT is present not only in animals and young children but also in human adults (5,6) has fueled attempts to exploit its energy-consuming property to counter obesity (7,8). Unfortunately, however, obese patients have insufficient amounts of BAT, limiting the value of constitutive BAT for weight reduction (9).On the other hand, obese subjects have abundant amounts WAT. It has recently become known that WAT can recruit clusters of adipocytes with a brownlike phenotype. This process, called WAT browning, can be seen in mice stimulated by prolonged cold exposure or by b3AR agonists as a mimetic of cold stress (10,11). Brownlike cells recruited by WAT browning are referred to as beige (pale brown) adipocytes (12)(13)...

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Section: Discussionsupporting

confidence: 61%

“…In identifying the mediators for increased 18 F-FDG uptake by b3AR stimulation, BAT displayed high expression of both GLUT4 and hexokinase-II regardless of treatment (Fig. 3).…”

Section: Glut4 and Hexokinase-ii Expression In Inguinal Watmentioning

confidence: 99%

Section: Acute Stimulation Of Interscapular Bat 18 F-fdg Uptakementioning

confidence: 99%

Section: Animal Preparation and Cl316243 Treatmentmentioning

confidence: 99%

mentioning

confidence: 99%

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¹⁸F-FDG PET/CT Monitoring of β3 Agonist–Stimulated Brown Adipocyte Recruitment in White Adipose Tissue

et al. 2014

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Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity

et al. 2023

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The angiotensin II type 2 receptor (AT2R) exerts vasorelaxant, anti‐inflammatory, and antioxidant properties. In obesity, its activation counterbalances the adverse cardiovascular effects of angiotensin II mediated by the AT1R. Preliminary results indicate that it also promotes brown adipocyte differentiation in vitro. Our hypothesis is that AT2R activation could increase BAT mass and activity in obesity. Five‐week‐old male C57BL/6J mice were fed a standard or a high‐fat (HF) diet for 6 weeks. Half of the animals were treated with compound 21 (C21), a selective AT2R agonist, (1 mg/kg/day) in the drinking water. Electron transport chain (ETC), oxidative phosphorylation, and UCP1 proteins were measured in the interscapular BAT (iBAT) and thoracic perivascular adipose tissue (tPVAT) as well as inflammatory and oxidative parameters. Differentiation and oxygen consumption rate (OCR) in the presence of C21 was tested in brown preadipocytes. In vitro, C21‐differentiated brown adipocytes showed an AT2R‐dependent increase of differentiation markers (Ucp1, Cidea, Pparg) and increased basal and H+ leak‐linked OCR. In vivo, HF‐C21 mice showed increased iBAT mass compared to HF animals. Both their iBAT and tPVAT showed higher protein levels of the ETC protein complexes and UCP1, together with a reduction of inflammatory and oxidative markers. The activation of the AT2R increases BAT mass, mitochondrial activity, and reduces markers of tissue inflammation and oxidative stress in obesity. Therefore, insulin reduction and better vascular responses are achieved. Thus, the activation of the protective arm of the renin–angiotensin system arises as a promising tool in the treatment of obesity.

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Dynamic contrast‐enhanced MRI of brown and beige adipose tissues

Yaligar

Verma

Gopalan

et al. 2019

Magnetic Resonance in Med

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Purpose The vascular blood flow in brown adipose tissue (BAT) is important for handling triglyceride clearance, increased blood flow and oxygenation. We used dynamic contrast‐enhanced (DCE)‐MRI and fat fraction (FF) imaging for investigating vascular perfusion kinetics in brown and beige adipose tissues with cold exposure or treatment with β3‐adrenergic agonist. Methods FF imaging and DCE‐MRI using gadolinium‐diethylenetriaminepentaacetic acid were performed in interscapular BAT (iBAT) and beige tissues using male Wister rats (n = 38). Imaging was performed at thermoneutral condition and with either cold exposure, treatment with pharmacological agent CL‐316,243, or saline. DCE‐MRI and FF data were co‐registered to enhance the understanding of metabolic activity. Results Uptake of contrast agent in activated iBAT and beige tissues were significantly (P < .05) higher than nonactivated iBAT. The Ktrans and kep increased significantly in iBAT and beige tissues after treatment with either cold exposure or β3‐adrenergic agonist. The FF decreased in activated iBAT and beige tissues. The Ktrans and FF from iBAT and beige tissues were inversely correlated (r = 0.97; r = 0.94). Significant increase in vascular endothelial growth factor expression and Ktrans in activated iBAT and beige tissues were in agreement with the increased vasculature and vascular perfusion kinetics. The iBAT and beige tissues were validated by measuring molecular markers. Conclusion Increased Ktrans and decreased FF in iBAT and beige tissues were in agreement with the vascular perfusion kinetics facilitating the clearance of free fatty acids. The methodology can be extended for the screening of browning agents.

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Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation

Cited by 74 publications

References 26 publications

¹⁸F-FDG PET/CT Monitoring of β3 Agonist–Stimulated Brown Adipocyte Recruitment in White Adipose Tissue

¹⁸F-FDG PET/CT Monitoring of β3 Agonist–Stimulated Brown Adipocyte Recruitment in White Adipose Tissue

Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity

Dynamic contrast‐enhanced MRI of brown and beige adipose tissues

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Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation

Cited by 74 publications

References 26 publications

18F-FDG PET/CT Monitoring of β3 Agonist–Stimulated Brown Adipocyte Recruitment in White Adipose Tissue

18F-FDG PET/CT Monitoring of β3 Agonist–Stimulated Brown Adipocyte Recruitment in White Adipose Tissue

Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity

Dynamic contrast‐enhanced MRI of brown and beige adipose tissues

Contact Info

Product

Resources

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¹⁸F-FDG PET/CT Monitoring of β3 Agonist–Stimulated Brown Adipocyte Recruitment in White Adipose Tissue

¹⁸F-FDG PET/CT Monitoring of β3 Agonist–Stimulated Brown Adipocyte Recruitment in White Adipose Tissue