scholarly journals A Differential Pattern of Batokine Expression in Perivascular Adipose Tissue Depots From Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Alberto Mestres-Arenas ◽  
Joan Villarroya ◽  
Marta Giralt ◽  
Francesc Villarroya ◽  
Marion Peyrou
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Thoracic Aorta ◽  
Abdominal Aorta ◽  
Vascular Function ◽  
Vascular System ◽  
Mesenteric Arteries ◽  
Fibroblast Growth Factor 21 ◽  
Perivascular Adipose Tissue ◽  
Brown Adipose

Depending on its anatomical placement, perivascular adipose tissue (PVAT) has been found to possess features more (e.g., aortic thoracic) or less (e.g., aortic abdominal) similar to brown/beige adipose tissue in mice, whereas PVAT surrounding the mesenteric arteries and the caudal part of abdominal aorta is similar to white fat. PVAT is thought to influence vascular function through the effects of adipose-secreted molecules on vessels. Brown adipose tissue was recently shown to play differential secretory role via secretion of the so-called batokines but the involvement of differential batokine production in PVAT brown/beige plasticity was unclear. The current study characterizes for the first time the expression of batokines at aortic thoracic PVAT (tPVAT) and aortic abdominal PVAT (aPVAT) in comparison with typical brown and white adipose depots, in basal and thermogenically activated conditions. We found that both PVAT depots increased their expression of genes encoding the batokines bone morphogenetic protein-8b (BMP8B), fibroblast growth factor-21 (FGF21), and kininogen-2 (KNG2) in response to cold, indicating that, under cold-induced thermogenic activation, both thoracic aorta and abdominal aorta would experience intense local exposure to these PVAT-secreted batokines. In contrast, the gene expression levels of growth/differentiation factor-15 and vascular endothelial growth factor-A were induced only in tPVAT. Under short-term high-fat diet-induced thermogenic activation, the thoracic aorta would be specifically exposed to a local increase in PVAT-originating BMP8B, FGF21, and KNG2. Our data support the notion that acquisition of a brown/beige phenotype in PVAT is associated with upregulation of batokines, mainly BMP8B, FGF21, and KNG2, that can differentially target the vascular system.

scholarly journals Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation

2011 ◽  
Vol 301 (4) ◽  
pp. H1425-H1437 ◽  
Author(s):  
Timothy P. Fitzgibbons ◽  
Sophia Kogan ◽  
Myriam Aouadi ◽  
Greg M. Hendricks ◽  
Juerg Straubhaar ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Immune Cell ◽  
Expression Profiles ◽  
Immunohistochemical Analysis ◽  
Macrophage Infiltration ◽  
Interscapular Brown Adipose Tissue ◽  
Perivascular Adipose Tissue ◽  
The Metabolic Syndrome ◽  
Brown Adipose

Thoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and the metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea, and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared with white adipose tissue (WAT), PVAT and BAT from C57BL6/J mice fed a high-fat diet for 13 wk had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80 and CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b+/CD11c+ macrophages in BAT (1.0%) compared with WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from inflammatory stress.

scholarly journals Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone

2021 ◽  
Vol 12 ◽  
Author(s):  
Yibin Wang ◽  
Fatima Yildiz ◽  
Andrey Struve ◽  
Mario Kassmann ◽  
Lajos Markó ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Vascular Tone ◽  
Mesenteric Arteries ◽  
Aging Effects ◽  
Perivascular Adipose Tissue ◽  
Kcnq Channels ◽  
Age Related ◽  
Cardiovascular Morbidity And Mortality

Aging is an independent risk factor for hypertension, cardiovascular morbidity, and mortality. However, detailed mechanisms linking aging to cardiovascular disease are unclear. We studied the aging effects on the role of perivascular adipose tissue and downstream vasoconstriction targets, voltage-dependent KV7 channels, and their pharmacological modulators (flupirtine, retigabine, QO58, and QO58-lysine) in a murine model. We assessed vascular function of young and old mesenteric arteries in vitro using wire myography and membrane potential measurements with sharp electrodes. We also performed bulk RNA sequencing and quantitative reverse transcription-polymerase chain reaction tests in mesenteric arteries and perivascular adipose tissue to elucidate molecular underpinnings of age-related phenotypes. Results revealed impaired perivascular adipose tissue-mediated control of vascular tone particularly via KV7.3–5 channels with increased age through metabolic and inflammatory processes and release of perivascular adipose tissue-derived relaxation factors. Moreover, QO58 was identified as novel pharmacological vasodilator to activate XE991-sensitive KCNQ channels in old mesenteric arteries. Our data suggest that targeting inflammation and metabolism in perivascular adipose tissue could represent novel approaches to restore vascular function during aging. Furthermore, KV7.3–5 channels represent a promising target in cardiovascular aging.

scholarly journals Inducible Loss of the Aryl Hydrocarbon Receptor Activates Perigonadal White Fat Respiration and Brown Fat Thermogenesis via Fibroblast Growth Factor 21

2019 ◽  
Vol 20 (4) ◽  
pp. 950 ◽  
Author(s):  
Nathaniel Girer ◽  
Dwayne Carter ◽  
Nisha Bhattarai ◽  
Mehnaz Mustafa ◽  
Larry Denner ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Aryl Hydrocarbon Receptor ◽  
Fibroblast Growth Factor ◽  
Knockout Mouse ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Knockout Mouse Model ◽  
Aryl Hydrocarbon ◽  
Brown Adipose

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor highly expressed in hepatocytes. Researchers have employed global and liver-specific conditional Ahr knockout mouse models to characterize the physiological roles of the AHR; however, the gestational timing of AHR loss in these models can complicate efforts to distinguish the direct and indirect effects of post-gestational AHR deficiency. Utilizing a novel tamoxifen-inducible AHR knockout mouse model, we analyzed the effects of hepatocyte-targeted AHR loss in adult mice. The data demonstrate that AHR deficiency significantly reduces weight gain and adiposity, and increases multilocular lipid droplet formation within perigonadal white adipose tissue (gWAT). Protein and mRNA expression of fibroblast growth factor 21 (FGF21), an important hepatokine that activates thermogenesis in brown adipose tissue (BAT) and gWAT, significantly increases upon AHR loss and correlates with a significant increase of BAT and gWAT respiratory capacity. Confirming the role of FGF21 in mediating these effects, this phenotype is reversed in mice concomitantly lacking AHR and FGF21 expression. Chromatin immunoprecipitation analyses suggest that the AHR may constitutively suppress Fgf21 transcription through binding to a newly identified xenobiotic response element within the Fgf21 promoter. The data demonstrate an important AHR-FGF21 regulatory axis that influences adipose biology and may represent a “druggable” therapeutic target for obesity and its related metabolic disorders.

scholarly journals Fibroblast Growth Factor-21, Leptin, and Adiponectin Responses to Acute Cold-Induced Brown Adipose Tissue Activation

2020 ◽  
Vol 105 (3) ◽  
pp. e520-e531 ◽  
Author(s):  
Lijuan Sun ◽  
Jianhua Yan ◽  
Hui Jen Goh ◽  
Priya Govindharajulu ◽  
Sanjay Verma ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Brown Adipose Tissue ◽  
Fibroblast Growth Factor ◽  
Cold Exposure ◽  
Maximum Temperature ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Adiponectin Concentration ◽  
Brown Adipose

Abstract Background Adipocyte-derived hormones play a role in insulin sensitivity and energy homeostasis. However, the relationship between circulating fibroblast growth factor 21 (FGF21), adipocytokines and cold-induced supraclavicular brown adipose tissue (sBAT) activation is underexplored. Objective Our study aimed to investigate the relationships between cold-induced sBAT activity and plasma FGF21 and adipocytokines levels in healthy adults. Design Nineteen healthy participants underwent energy expenditure (EE) and supraclavicular infrared thermography (IRT) within a whole-body calorimeter at baseline and at 2 hours post-cold exposure. 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scans were performed post-cold exposure. PET sBAT mean standardized uptake value (SUV mean), MR supraclavicular fat fraction (sFF), anterior supraclavicular maximum temperature (Tscv max) and EE change (%) after cold exposure were used to quantify sBAT activity. Main Outcome Measures Plasma FGF21, leptin, adiponectin, and tumor necrosis factor alpha (TNFα) at baseline and 2 hours post-cold exposure. Body composition at baseline by dual-energy x-ray absorptiometry (DXA). Results Plasma FGF21 and adiponectin levels were significantly reduced after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Leptin concentration was significantly reduced in both BAT-positive and BAT-negative participants after cold exposure. Adiponectin concentration at baseline was positively strongly associated with sBAT PET SUV mean (coefficient, 3269; P = 0.01) and IRT Tscv max (coefficient, 6801; P  = 0.03), and inversely correlated with MR sFF (coefficient, −404; P  = 0.02) after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Conclusion Higher adiponectin concentrations at baseline indicate a greater cold-induced sBAT activity, which may be a novel predictor for sBAT activity in healthy BAT-positive adults. Highlights A higher adiponectin concentration at baseline was associated with higher cold-induced supraclavicular BAT PET SUV mean and IRT Tscv max, and lower MR supraclavicular FF. Adiponectin levels maybe a novel predictor for cold-induced sBAT activity.

Fibroblast growth factor-21 is expressed in neonatal and pheochromocytoma-induced adult human brown adipose tissue

Metabolism ◽  
2014 ◽  
Vol 63 (3) ◽  
pp. 312-317 ◽  
Author(s):  
Elayne Hondares ◽  
José M. Gallego-Escuredo ◽  
Pavel Flachs ◽  
Andrea Frontini ◽  
Ruben Cereijo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Brown Adipose Tissue ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Adult Human ◽  
Brown Adipose

An endocrine role for brown adipose tissue?

2013 ◽  
Vol 305 (5) ◽  
pp. E567-E572 ◽  
Author(s):  
Joan Villarroya ◽  
Rubén Cereijo ◽  
Francesc Villarroya
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Brown Adipose Tissue ◽  
Metabolic Diseases ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Fibroblast Growth Factor 21 ◽  
Current View ◽  
Brown Adipose ◽  
Endocrine Factors

White adipose tissue is recognized as both a site of energy storage and an endocrine organ that produces a myriad of endocrine factors called adipokines. Brown adipose tissue (BAT) is the main site of nonshivering thermogenesis in mammals. The amount and activity of brown adipocytes are associated with protection against obesity and associated metabolic alterations. These effects of BAT are traditionally attributed to its capacity for the oxidation of fatty acids and glucose to sustain thermogenesis. However, recent data suggest that the beneficial effects of BAT could involve a previously unrecognized endocrine role through the release of endocrine factors. Several signaling molecules with endocrine properties have been found to be released by brown fat, especially under conditions of thermogenic activation. Moreover, experimental BAT transplantation has been shown to improve glucose tolerance and insulin sensitivity mainly by influencing hepatic and cardiac function. It has been proposed that these effects are due to the release of endocrine factors by brown fat, such as insulin-like growth factor I, interleukin-6, or fibroblast growth factor-21. Further research is needed to determine whether brown fat plays an endocrine role and, if so, to comprehensively identify which endocrine factors are released by BAT. Such research may reveal novel clues for the observed association between brown adipocyte activity and a healthy metabolic profile, and it could also enlarge a current view of potential therapeutic tools for obesity and associated metabolic diseases.

Abstract 138: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Rho Kinase.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Aurelie Nguyen Dinh Cat ◽  
Tayze T Antunes ◽  
Glaucia E Callera ◽  
Augusto C Montezano ◽  
Ying He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Mesenteric Arteries ◽  
Mineralocorticoid Receptors ◽  
Resistance Arteries ◽  
Brown Adipose

Aldosterone (aldo) plays a role in cardiovascular diseases, including hypertension and obesity. We previously demonstrated that adipocyte-derived factors regulate vascular function and cell signaling in cultured vascular smooth muscle cells. Moreover, adipocytes are able to produce aldo, which influences vascular reactivity. Plasma levels of aldo are positively correlated with obesity and hypertension. However, the pathophysiological role of aldo and mineralocorticoid receptors (MR) in adipose tissue and its interactions with the vasculature remains elusive. In our study, we investigated molecular mechanisms whereby activation of MR, in adipocytes, leads to release of vascular reactive factors and regulation of vascular tone, using a conditional transgenic mouse model that overexpresses MR only in the adipocytes. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (DT) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in DT or control mice. However, in the presence of Fcm from DT mice, relaxation to Ach was impaired in control mice (Ach 10 -6 M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (anti-oxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from DT mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm CT vs. 1.7±0.2 mN/mm DT, p<0.05). Phosphorylation of ezrin, a marker of Rho kinase activation, measured by immunoblotting, was decreased in white and brown adipose tissues of DT (CT: 3.1±0.7 vs. DT: 0.6±0.1, arbitrary units, p<0.05). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, and may be involved in vascular oxidative stress. MR in adipocytes is also important to the anti-contractile properties of the adipose tissue through downregulation of Rho kinase signaling. Our study identiy novel mechanisms linking vascular and adipose biology through adipocyte MRs.

Abstract P061: Identification Of Piezo1 Channels In Perivascular Adipose Tissue (pvat) And Their Potential Role In Vascular Function

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Taylor Miron ◽  
Emma D Flood ◽  
Marie Negron ◽  
Janice Thompson ◽  
Stephanie W Watts
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Mrna Level ◽  
Stromal Vascular Fraction ◽  
Mesenteric Arteries ◽  
Human Artery ◽  
Mesenteric Vessel ◽  
Perivascular Adipose Tissue ◽  
Isolated Aorta ◽  
Aortic Contraction

The vasculature constantly experiences distension/pressure exerted by the blood and responds accordingly to maintain homeostasis. Perivascular adipose tissue (PVAT) is gaining support as a formal blood vessel layer and also experiences these changes. We hypothesized that activation of the mechanotransducer Piezo1 directly increases vascular contraction in a way that might be modified by PVAT. The presence of Piezo1 was investigated at the mRNA level via PCR; protein via immunohistochemistry; and contractility via isolated tissue bath. Rat superior and mesenteric arteries, thoracic aortae, human mesenteric vessels and their PVATs were studied. Piezo1 mRNA (beta2 microglobulin calibrator) was expressed in the aortic vessel (2 -ΔC T =0.011); aortic PVAT (2 -ΔC T =0.0172); mesenteric vessel (2 -ΔC T =.00302), and mesenteric PVAT (2 -ΔC T =0.0219). Both adipocytes (2 -ΔC T =0.0249) and stromal vascular fraction (2 -ΔC T =0.0159) of mesenteric PVAT expressed Piezo1 mRNA. Piezo1 mRNA expression was greater in magnitude (one-way ANOVA) than that of the mechanotransducers Piezo2, TRPV4, TMEM16, and Panx1. Piezo1 protein was present in rat aortic PVAT, rat mesenteric (mes) artery, vein, and PVAT, as well as in human artery, vein, and PVAT. The Piezo1 agonists Yoda and Jedi (1 nM - 10 μM) did not stimulate rat aortic contraction [max <10% phenylephrine (PE) 10 μM contraction] or relaxation independent from vehicle in tissues + or - PVAT (relaxation as % of half maximal PE contraction was: Veh-PVAT=45.3±7.0; Yoda-PVAT=46.7±25.6; Jedi-PVAT= 40.4±10.3; Veh+PVAT= 71.8±19.7; Jedi+PVAT=39.1±13.2; Yoda +PVAT=21.6±10.9). Slightly K+ depolarizing the aorta did not unmask contraction to Yoda. Finally, the Piezo1 antagonist Dooku [10 μM] did not shift the PE curve (-log EC50 values [M]: Veh-PVAT= 7.96±0.12; Dooku-PVAT=7.26±0.22, Veh+PVAT=7.29±0.08; Dooku+PVAT=6.96±0.07). Surprisingly, Dooku [10 μM] directly caused aortic contraction in the absence of PVAT (Dooku 27.2±11.7 vs vehicle 13.5±11.2 %PE contraction), but not in the presence of PVAT vs vehicle (Dooku 2.9±1.9 vs Vehicle 7.3±5.2% PE contraction). Thus, Piezo1 is present and functional in the isolated aorta, important knowledge given that this molecule may serve as a translator of vascular pressure.

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