scholarly journals Perivascular Adipose Tissue: Quantitative analysis by morphometry and stereology in rodents

2019 ◽  
Author(s):  
Felipe Demani Carneiro ◽  
Stephanie Christinne Sinder Mello ◽  
Emiliana Barbosa Marques ◽  
Rogerio Barbosa Magalhaes Barros ◽  
Christianne Bretas Vieira Scaramello ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Droplet Diameter ◽  
Volume Density ◽  
Brown Adipocytes ◽  
Perivascular Adipose Tissue ◽  
Know How ◽  
Morphological Aspects ◽  
White Adipocytes ◽  
Male Wistar Rats ◽  
Vascular Physiology

ABSTRACTThe perivascular adipose tissue (PVAT) provides mechanical support to blood vessels and modulates vascular physiology in obesity. Our goal is to provide a reproductive protocol using morphometric and stereological tools to assess PVAT morphology. The thoracic aorta from male Wistar rats (n=6) and C57BL/6 mice (n=7) underwent routine histological procedures, and two independent observers analyzed the same set of digital images. Agreement and reproducibility were assessed. Both observers showed that the diameter of rat brown adipocytes is larger than mice (P<0.002) as expected, and that the number density (QA) of brown adipocytes is smaller in rats compared to mice (P<0.01). Considering lipid droplets, observer #1 reported that in rats they were larger (P<0.005) and had a higher volume density (VV) than mice (P=0.035), but observer #2 found the opposite for lipid droplet diameter (P=0.001). White adipocytes were not found in the PVAT. Bland-Altman plots demonstrated agreement and reproducibility between observers since the means are close to the main difference (bias) and within the 95% limits of agreement. In conclusion, the methodology proposed can quantify morphological aspects of the aorta PVAT in rodents. It is reproducible and can be performed by both expert and inexperienced researchers, once they know how to recognize the structures of interest to be measured.

scholarly journals SIRT3 (Sirtuin-3) Prevents Ang II (Angiotensin II)–Induced Macrophage Metabolic Switch Improving Perivascular Adipose Tissue Function

2020 ◽  
Author(s):  
Tong Wei ◽  
Jing Gao ◽  
Chenglin Huang ◽  
Bei Song ◽  
Mengwei Sun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Metabolic Phenotype ◽  
Inflammasome Activation ◽  
Ang Ii ◽  
Sirtuin 3 ◽  
Metabolic Switch ◽  
Brown Adipocytes ◽  
Perivascular Adipose Tissue

Objective: Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the perivascular adipose tissue microenvironment of hypertensive mice. However, the role of macrophages in initiating metabolic inflammation remains uncertain. SIRT3 (sirtuin-3), a NAD-dependent deacetylase, is sensitive to metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated metabolic shift in regulating NLRP3 (Nod-like receptor family pyrin domain-containing 3) inflammasome activation. Approach and Results: Here, we report that Ang II (angiotensin II) accelerates perivascular adipose tissue inflammation and fibrosis, accompanied by NLRP3 inflammasome activation and IL (interleukin)-1β secretion in myeloid SIRT3 knockout (SIRT3 − / − ) mice. This effect is associated with adipose tissue mitochondrial dysfunction. In vitro studies indicate that the deletion of SIRT3 in bone marrow–derived macrophages induces IL-1β production by shifting the metabolic phenotype from oxidative phosphorylation to glycolysis. Mechanistically, SIRT3 deacetylates and activates PDHA1 (pyruvate dehydrogenase E1 alpha) at lysine 83, and the loss of SIRT3 leads to PDH activity decrease and lactate accumulation. Knocking down LDHA (lactate dehydrogenase A) or using carnosine, a buffer against lactic acid, attenuates IL-1β secretion. Furthermore, the blockade of IL-1β from macrophages into brown adipocytes restores thermogenic markers and mitochondrial oxygen consumption. Moreover, NLRP3 knockout (NLRP3 −/− ) mice exhibited reduced IL-1β production while rescuing the mitochondrial function of brown adipocytes and alleviating perivascular adipose tissue fibrosis. Conclusions: SIRT3 represents a potential therapeutic target to attenuate NLRP3-related inflammation. Pharmacological targeting of glycolytic metabolism may represent an effective therapeutic approach.

scholarly journals Role of Perivascular Adipose Tissue in Vascular Physiology and Pathology

Hypertension ◽  
2017 ◽  
Vol 69 (5) ◽  
pp. 770-777 ◽  
Author(s):  
Zhen Fang Huang Cao ◽  
Elina Stoffel ◽  
Paul Cohen
Keyword(s):  
Adipose Tissue ◽  
Perivascular Adipose Tissue ◽  
Vascular Physiology

scholarly journals Peroxisome Proliferator-Activated Receptors-α and -γ, and cAMP-Mediated Pathways, Control Retinol-Binding Protein-4 Gene Expression in Brown Adipose Tissue

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1162-1173 ◽  
Author(s):  
Meritxell Rosell ◽  
Elayne Hondares ◽  
Sadahiko Iwamoto ◽  
Frank J. Gonzalez ◽  
Martin Wabitsch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Retinol Binding Protein ◽  
Peroxisome Proliferator ◽  
Brown Adipocytes ◽  
Retinol Binding Protein 4 ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Rbp4 Gene

Retinol binding protein-4 (RBP4) is a serum protein involved in the transport of vitamin A. It is known to be produced by the liver and white adipose tissue. RBP4 release by white fat has been proposed to induce insulin resistance. We analyzed the regulation and production of RBP4 in brown adipose tissue. RBP4 gene expression is induced in brown fat from mice exposed to cold or treated with peroxisome proliferator-activated receptor (PPAR) agonists. In brown adipocytes in culture, norepinephrine, cAMP, and activators of PPARγ and PPARα induced RBP4 gene expression and RBP4 protein release. The induction of RBP4 gene expression by norepinephrine required intact PPAR-dependent pathways, as evidenced by impaired response of the RBP4 gene expression to norepinephrine in PPARα-null brown adipocytes or in the presence of inhibitors of PPARγ and PPARα. PPARγ and norepinephrine can also induce the RBP4 gene in white adipocytes, and overexpression of PPARα confers regulation by this PPAR subtype to white adipocytes. The RBP4 gene promoter transcription is activated by cAMP, PPARα, and PPARγ. This is mediated by a PPAR-responsive element capable of binding PPARα and PPARγ and required also for activation by cAMP. The induction of the RBP4 gene expression by norepinephrine in brown adipocytes is protein synthesis dependent and requires PPARγ-coactivator-1-α, which acts as a norepinephine-induced coactivator of PPAR on the RBP4 gene. We conclude that PPARγ- and PPARα-mediated signaling controls RBP4 gene expression and releases in brown adipose tissue, and thermogenic activation induces RBP4 gene expression in brown fat through mechanisms involving PPARγ-coactivator-1-α coactivation of PPAR signaling.

Brown adipocytes postnatally arise through both differentiation from progenitors and conversion from white adipocytes in Syrian hamster

2018 ◽  
Vol 124 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Yuko Okamatsu-Ogura ◽  
Junko Nio-Kobayashi ◽  
Kazuki Nagaya ◽  
Ayumi Tsubota ◽  
Kazuhiro Kimura
Keyword(s):  
Adipose Tissue ◽  
Lipid Droplets ◽  
Brown Adipocyte ◽  
Fat Tissue ◽  
Brown Adipocytes ◽  
Syrian Hamsters ◽  
Monocarboxylate Transporter 1 ◽  
White Adipocytes ◽  
Proliferation And Differentiation ◽  
Adipocyte Progenitors

To investigate the postnatal development of brown adipose tissue (BAT) in Syrian hamsters, we histologically examined interscapular fat tissue from 5–16-day-old pups, focusing on how brown adipocytes arise. Interscapular fat of 5-day-old hamsters mainly consisted of white adipocytes containing large unilocular lipid droplets, as observed in typical white adipose tissue (WAT). On day 7, clusters of small, proliferative nonadipocytes with a strong immunoreactivity for Ki67 appeared near the edge of the interscapular fat tissue. The area of the Ki67-positive regions expanded to ~50% of the total tissue area by day 10. The interscapular fat showed the typical BAT feature by day 16. A brown adipocyte-specific marker, uncoupling protein-1, was clearly detected on day 10 and thereafter, while not detected on day 7. During conversion of interscapular fat from WAT to BAT, unilocular adipocytes completely and rapidly disappeared without obvious apoptosis. Dual immunofluorescence staining for Ki67 and monocarboxylate transporter 1 (MCT1), another selective marker for brown adipocytes, revealed that most of the proliferating cells were of the brown adipocyte lineage. Electron microscopic examination showed that some of the white adipocytes contained small lipid droplets in addition to the large droplet and expressed MCT1 as do progenitor and mature brown adipocytes, implying a direct conversion from white to brown adipocytes. These results suggest that BAT of Syrian hamsters develops postnatally through two different pathways: the proliferation and differentiation of brown adipocyte progenitors and the conversion of unilocular adipocytes to multilocular brown adipocytes. NEW & NOTEWORTHY Brown and white adipose tissues (BAT and WAT, respectively) are quite different in morphological features and function; however, the boundary between these tissues is obscure. In this study, we histologically evaluated the process of BAT development in Syrian hamsters, which shows postnatal conversion of WAT to BAT. Our results suggest that brown adipocytes arise through two different pathways: the proliferation and differentiation of brown adipocyte progenitors and the conversion from white adipocytes.

Seeing the trees in the forest: selective electroporation of adipocytes within adipose tissue

2004 ◽  
Vol 287 (3) ◽  
pp. E574-E582 ◽  
Author(s):  
James G. Granneman ◽  
Pipeng Li ◽  
Yuyan Lu ◽  
Jacqueline Tilak
Keyword(s):  
Adipose Tissue ◽  
Adrenergic Receptor ◽  
Fat Cells ◽  
Subcellular Targeting ◽  
In Vivo Electroporation ◽  
Brown Adipocytes ◽  
Adrenergic Signaling ◽  
Large Size ◽  
White Adipocytes

Electroporation has been recently adapted for the transfer of macromolecules into cells of tissues in vivo. Although mature adipocytes constitute <20% of cells residing in adipose tissue, we hypothesized that fat cells might be susceptible to selective electrotransfer of plasmid DNA owing to their large size relative to other cells in the tissue. Results demonstrate the feasibility of electroporating DNA into mature fat cells with >99% selectivity over other cells in the tissue. Further experiments used the “adiporation” technique to image the subcellular targeting of fluorescent bioreporter molecules to the nucleus, mitochondria, and lipid droplets of adipocytes within intact adipose tissue. Finally, we utilized fluorescent bioreporters to examine the effects of constitutive activation of the β-adrenergic signaling pathway in adipocytes. These results demonstrate that overexpression of rat β1-adrenergic receptors alters the cellular morphology of white adipocytes in a fashion that mimics the effects of systemic infusion of β3-adrenergic receptor agonists. Hallmarks of the altered morphology include pronounced fragmentation of the single lipid droplet, repositioning of the nucleus, and induction of mitochondrial biogenesis. These results indicate that activation of β-adrenergic signaling within adipocytes is sufficient to induce a phenotype that resembles typical brown adipocytes and suggest that in vivo electroporation will allow molecular dissection of the mechanisms involved.

Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes

2000 ◽  
Vol 279 (3) ◽  
pp. C670-C681 ◽  
Author(s):  
J. Himms-Hagen ◽  
A. Melnyk ◽  
M. C. Zingaretti ◽  
E. Ceresi ◽  
G. Barbatelli ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Protein ◽  
Protein Composition ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Bat Mitochondria ◽  
Adrenoceptor Agonist ◽  
Brown Adipose ◽  
A Cell

Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the β3-adrenoceptor agonist, CL-316243 (CL). Objectives were to determine whether these multilocular adipocytes derived from cells that already existed in the WAT or from proliferation of precursor cells and whether new mitochondria contained in them were typical brown adipocyte mitochondria. Use of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL treatment showed that most multilocular cells derived from cells already present in the WAT. Morphological techniques showed that at least a subpopulation of unilocular adipocytes underwent conversion to multilocular mitochondria-rich adipocytes. A small proportion of multilocular adipocytes (∼8%) was positive for UCP1 by immunohistochemistry. Biochemical techniques showed that mitochondrial protein recovered from WAT increased 10-fold and protein isolated from brown adipose tissue (BAT) doubled in CL-treated rats. Stained gels showed a different protein composition of new mitochondria isolated from WAT from that of mitochondria isolated from BAT. Western blotting showed new mitochondria in WAT to contain both UCP1, but at a much lower concentration than in BAT mitochondria, and UCP3, at a higher concentration than that in BAT mitochondria. We hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins. First, most come from convertible unilocular adipocytes that become multilocular and make many mitochondria that contain UCP3. Second, some come from a cell that gives rise to more typical brown adipocytes that express UCP1.

scholarly journals Perirenal Adipose Tissue—Current Knowledge and Future Opportunities

2021 ◽  
Vol 10 (6) ◽  
pp. 1291
Author(s):  
Adriana Grigoraș ◽  
Raluca Anca Balan ◽  
Irina-Draga Căruntu ◽  
Simona Eliza Giușcă ◽  
Ludmila Lozneanu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tumor Progression ◽  
Current Knowledge ◽  
Inflammatory Cells ◽  
Close Correlation ◽  
Renal Diseases ◽  
Brown Adipocytes ◽  
Perirenal Adipose Tissue ◽  
White Adipocytes ◽  
Visceral Adipose

The perirenal adipose tissue (PRAT), a component of visceral adipose tissue, has been recently recognized as an important factor that contributes to the maintenance of the cardiovascular system and kidney homeostasis. PRAT is a complex microenvironment consisting of a mixture of white adipocytes and dormant and active brown adipocytes, associated with predipocytes, sympathetic nerve endings, vascular structures, and different types of inflammatory cells. In this review, we summarize the current knowledge about PRAT and discuss its role as a major contributing factor in the pathogenesis of hypertension, obesity, chronic renal diseases, and involvement in tumor progression. The new perspectives of PRAT as an endocrine organ and recent knowledge regarding the possible activation of dormant brown adipocytes are nowadays considered as new areas of research in obesity, in close correlation with renal and cardiovascular pathology. Supplementary PRAT complex intervention in tumor progression may reveal new pathways involved in carcinogenesis and, implicitly, may identify additional targets for tailored cancer therapy.

scholarly journals Adipocytes and Stromal Cells Regulate Brown Adipogenesis Through Secretory Factors During the Postnatal White-to-Brown Conversion of Adipose Tissue in Syrian Hamsters

2021 ◽  
Vol 9 ◽  
Author(s):  
Junnosuke Mae ◽  
Kazuki Nagaya ◽  
Yuko Okamatsu-Ogura ◽  
Ayumi Tsubota ◽  
Shinya Matsuoka ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Syrian Hamsters ◽  
White Adipocytes ◽  
Adipocyte Progenitors ◽  
Mapk Signaling Pathways ◽  
Brown Adipogenesis

Brown adipose tissue (BAT) is a specialized tissue that regulates non-shivering thermogenesis. In Syrian hamsters, interscapular adipose tissue is composed primarily of white adipocytes at birth, which is converted to BAT through the proliferation and differentiation of brown adipocyte progenitors and the simultaneous disappearance of white adipocytes. In this study, we investigated the regulatory mechanism of brown adipogenesis during postnatal BAT formation in hamsters. Interscapular adipose tissue of a 10-day-old hamster, which primarily consists of brown adipocyte progenitors and white adipocytes, was digested with collagenase and fractioned into stromal–vascular (SV) cells and white adipocytes. SV cells spontaneously differentiated into brown adipocytes that contained multilocular lipid droplets and expressed uncoupling protein 1 (Ucp1), a marker of brown adipocytes, without treatment of adipogenic cocktail such as dexamethasone and insulin. The spontaneous differentiation of SV cells was suppressed by co-culture with adipocytes or by the addition of white adipocyte-conditioned medium. Conversely, the addition of SV cell-conditioned medium increased the expression of Ucp1. These results indicate that adipocytes secrete factors that suppress brown adipogenesis, whereas SV cells secrete factors that promote brown adipogenesis. Transcriptome analysis was conducted; however, no candidate suppressing factors secreted from adipocytes were identified. In contrast, 19 genes that encode secretory factors, including bone morphogenetic protein (BMP) family members, BMP3B, BMP5, and BMP7, were highly expressed in SV cells compared with adipocytes. Furthermore, the SMAD and MAPK signaling pathways, which represent the major BMP signaling pathways, were activated in SV cells, suggesting that BMPs secreted from SV cells induce brown adipogenesis in an autocrine manner through the SMAD/MAPK signaling pathways. Treatment of 5-day-old hamsters with type I BMP receptor inhibitor, LDN-193189, for 5 days reduced p38 MAPK phosphorylation and drastically suppressed BAT formation of interscapular adipose tissue. In conclusion, adipocytes and stromal cells regulate brown adipogenesis through secretory factors during the postnatal white-to-brown conversion of adipose tissue in Syrian hamsters.

scholarly journals Site-specific impairment of perivascular adipose tissue on advanced atherosclerotic plaques using multimodal nonlinear optical imaging

2019 ◽  
Vol 116 (36) ◽  
pp. 17765-17774 ◽  
Author(s):  
Suho Kim ◽  
Eun-Soo Lee ◽  
Sang-Won Lee ◽  
Yong-Hoon Kim ◽  
Chul-Ho Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Nonlinear Optical ◽  
Brown Fat ◽  
Atherosclerotic Plaques ◽  
Label Free ◽  
Perivascular Adipose Tissue ◽  
Site Specific ◽  
Knockout Mouse Model ◽  
Initial Stage ◽  
Vascular Physiology

Perivascular adipose tissue (PVAT), as a mechanical support, has been reported to systemically regulate vascular physiology by secreting adipokines and cytokines. How PVAT spatially and locally changes as atherosclerosis progresses is not known, however. We aimed to reveal the molecular changes in PVAT in advanced atherosclerosis based on multimodal nonlinear optical (MNLO) imaging. First, using an atherogenic apolipoprotein E knockout mouse model, we precisely assessed the browning level of thoracic PVAT via a correlative analysis between the size and number of lipid droplets (LDs) of label-free MNLO images. We also biochemically demonstrated the increased level of brown fat markers in the PVAT of atherosclerosis. In the initial stage of atherosclerosis, the PVAT showed a highly activated brown fat feature due to the increased energy expenditure; however, in the advanced stage, only the PVAT in the regions of the atherosclerotic plaques, not that in the nonplaque regions, showed site-specific changes. We found that p-smad2/3 and TGF-β signaling enhanced the increase in collagen to penetrate the PVAT and the agglomeration of LDs only at the sites of atherosclerotic plaques. Moreover, atherosclerotic thoracic PVAT (tPVAT) was an increased inflammatory response. Taken together, our findings show that PVAT changes differentially from the initial stages to advanced stages of atherosclerosis and undergoes spatial impairment focused on atherosclerotic plaques. Our study may provide insight into the local control of PVAT as a therapeutic target.

scholarly journals The Inhibition of Ureteral Motility by Periureteral Adipose Tissue

ISRN Urology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7
Author(s):  
Lyndsey M. Killian ◽  
Stuart J. Bund
Keyword(s):  
Nitric Oxide ◽  
Adipose Tissue ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase Inhibitor ◽  
Perivascular Adipose Tissue ◽  
Contractile Responses ◽  
Tissue Removal ◽  
Male Wistar Rats ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Perivascular adipose tissue exerts an anticontractile influence on vascular smooth muscle. This study was conducted to determine whether periureteral adipose tissue (PUAT) could exert a similar influence upon ureteral smooth muscle. Acetylcholine-stimulated (10−7 M–10−4 M) contractile responses of ureteral segments obtained from male Wistar rats were recorded in the presence and absence of PUAT. Ureters with PUAT generated phasic contractile responses with significantly lower frequencies () and magnitudes () compared with ureters cleared of their periureteral adipose tissue. Removal of PUAT significantly increased the frequency () and magnitude () of the contractile responses. Bioassay experiments demonstrated that ureters with PUAT released a transferable factor that significantly reduced frequencies (), but not magnitudes, of the contractile responses of ureters cleared of PUAT. The nitric oxide synthase inhibitor L-NNA (10−4 M) did not significantly influence the anticontractile effect exerted by ureters with PUAT. This is the first study to demonstrate that ureteral motility is influenced by its surrounding adipose tissue. The PUAT has an anticontractile effect which is mediated by a transferable factor released from the PUAT. The identity of the factor is unknown but does not exert its effect through nitric oxide.

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