Cold Exposure Differentially Stimulates Angiogenesis in BAT and WAT of Mice: Implication in Adrenergic Activation

Luo, Xiao; Jia, Ru; Luo, Xiaoqin; Wang, Guan; Zhang, Qiangling; Qiao, Hu; Wang, Nan; Yan, Jiaqi

doi:10.1159/000478680

Cited by 18 publications

(17 citation statements)

References 39 publications

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“…We examined the vasculatures in the inguinal WAT of the cold-challenged wild-type mice, labeled by the intravenously injected fluorescent Isolectin. In line with previous studies [29] , [30] , there was a significant increase in the vascular density as early as 3 days after the cold challenge ( Figure 3 A). Detailed quantification showed that the density of the vasculatures in the inguinal WAT was 867 ± 73 μm per mm 3 at 0 day, 1551 ± 99 μm per mm 3 at 3 days, 2048 ± 112 μm per mm 3 at 5 days, 2309 ± 138 μm per mm 3 at 7 days, and 2539 ± 126 μm per mm 3 at 10 days after the cold challenge ( Figure 3 B).…”

Section: Resultssupporting

confidence: 92%

Three-dimensional volume fluorescence-imaging of vascular plasticity in adipose tissues

Cao

Wang

et al. 2018

Molecular Metabolism

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ObjectiveThe vascular system is central to sustaining tissue survival and homeostasis. Blood vessels are densely present in adipose tissues and exert essential roles in their metabolism. However, conventional immunohistochemistry methods have intrinsic limitations in examining the 3D vascular network in adipose tissues as well as other organs in general.MethodsWe established a 3D volume fluorescence-imaging technique to visualize the vasculatures in mouse adipose tissues by combining the optimized steps of whole-mount immunolabeling, tissue optical clearing, and lightsheet volume fluorescence-imaging. To demonstrate the strength of this novel imaging procedure, we comprehensively assessed the intra-adipose vasculatures under obese conditions or in response to a cold challenge.ResultsWe show the entirety of the vascular network in mouse adipose tissues on the whole-tissue level at a single-capillary resolution for the first time in the field. We accurately quantify the pathological changes of vasculatures in adipose tissues in wild-type or obese mice (ob/ob, db/db, or diet-induced obesity). In addition, we identify significant and reversible changes of the intra-adipose vasculatures in the mice subjected to cold challenge (i.e., 4°). Furthermore, we demonstrate that the cold-induced vascular plasticity depends on the sympathetic-derived catecholamine signal and is involved in the beiging process of white adipose tissues.ConclusionsWe report a 3D volume fluorescence-imaging procedure that is compatible with many areas of vascular research and is poised to serve the field in future investigations of the vascular system in adipose tissues or other research scenarios.

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Section: Resultssupporting

confidence: 92%

Three-dimensional volume fluorescence-imaging of vascular plasticity in adipose tissues

Cao

Wang

et al. 2018

Molecular Metabolism

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“…Our results are in agreement with earlier studies that show transient increase in VEGF in brown adipocytes with BAT activation . The long‐term sympathetic nervous system stimulation either by cold exposure or by β3‐adrenergic agonist administration promote the secretion of VEGF for the transformation of WAT into beige adipose tissue . The VEGF secretion stimulates the proliferation of vascular endothelial cells for adequate expansion of vasculature network in browning adipose tissue.…”

Section: Discussionsupporting

confidence: 93%

“…62,63 The long-term sympathetic nervous system stimulation either by cold exposure or by β3-adrenergic agonist administration promote the secretion of VEGF for the transformation of WAT into beige adipose tissue. [63][64][65] The VEGF secretion stimulates the proliferation of vascular endothelial cells for adequate expansion of vasculature network in browning adipose tissue. The VEGF expression from inguinal beige adipose tissue increased by ~2-fold, which confirms the establishment of adequate vasculature stimulated by β3-adrenergic agonist intervention.…”

Section: Discussionmentioning

confidence: 99%

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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“…Therefore, we suggest that post mortem visualization of the I-BAT vessels gives better results compared to in vivo methods where native adipose 3 BioMed Research International tissue blocks the vessels' resolution (unpublished results). Vascular thickness or density is often studied with regard to the angiogenesis of WAT or BAT [22] or in metabolism studies [23]. Such studies rarely include anatomical details about vascular diameters; rather, they provide only information about vascular density [6].…”

Section: Discussionmentioning

confidence: 99%

Morphology of the Vasculature and Blood Supply of the Brown Adipose Tissue Examined in an Animal Model by Micro‐CT

Mrzílková

Michenka

Šeremeta

et al. 2020

BioMed Research International

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We performed micro-CT imaging of the vascular blood supply in the interscapular area of the brown adipose tissue in three mice with the use of intravascular contrast agent Aurovist™. Resulting 3D data rendering was then adapted into 2D resolution with visualization using false color system and grayscale images. These were then studied for the automatic quantification of the blood vessel density within this area. We found the highest most occurring density within arterioles or venules representing smaller blood vessels whereas with the increase of the vessel diameters a lower percentage rate of their presence was observed in the sample. Our study shows that micro-CT scanning in combination with Aurovist™ contrast is suitable for anatomical studies of interscapular area of brown adipose tissue blood vessel supply.

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Cold Exposure Differentially Stimulates Angiogenesis in BAT and WAT of Mice: Implication in Adrenergic Activation

Cited by 18 publications

References 39 publications

Three-dimensional volume fluorescence-imaging of vascular plasticity in adipose tissues

Three-dimensional volume fluorescence-imaging of vascular plasticity in adipose tissues

Dynamic contrast‐enhanced MRI of brown and beige adipose tissues

Morphology of the Vasculature and Blood Supply of the Brown Adipose Tissue Examined in an Animal Model by Micro‐CT

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