Hydrogen-sulfide-mediated vasodilatory effect of nucleoside 5′-monophosphorothioates in perivascular adipose tissue

2015 ◽  
Vol 93 (7) ◽  
pp. 585-595 ◽  
Author(s):  
Jerzy Bełtowski ◽  
Andrzej Guranowski ◽  
Anna Jamroz-Wiśniewska ◽  
Andrzej Wolski ◽  
Krzysztof Hałas

Hydrogen sulfide (H2S) is synthesized in perivascular adipose tissue (PVAT) and induces vasorelaxation. We examined whether the sulfur-containing AMP and GMP analogs AMPS and GMPS can serve as the H2S donors in PVAT. H2S production by isolated rat periaortic adipose tissue (PAT) was measured with a polarographic sensor. In addition, phenylephrine-induced contractility of aortic rings with (+) or without (−) PAT was examined. Isolated PAT produced H2S from AMPS or GMPS in the presence of the P2X7 receptor agonist BzATP. Phenylephrine-induced contractility of PAT(+) rings was lower than of PAT(−) rings. AMPS or GMPS had no effect on the contractility of PAT(−) rings, but used together with BzATP reduced the contractility of PAT(+) rings when endogenous H2S production was inhibited with propargylglycine. A high-fat diet reduced endogenous H2S production by PAT. Interestingly, AMPS and GMPS were converted to H2S by PAT of obese rats, and reduced contractility of PAT(+) aortic rings isolated from these animals even in the absence of BzATP. We conclude that (i) AMPS and GMPS can be hydrolyzed to H2S by PAT when P2X7 receptors are activated, (ii) a high-fat diet impairs endogenous H2S production by PAT, (iii) AMPS and GMPS restore the anticontractile effects of PAT in obese animals without P2X7 stimulation.

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1552
Author(s):  
Jozef Torok ◽  
Anna Zemancikova ◽  
Zuzana Valaskova ◽  
Peter Balis

The aim of the current study was to evaluate the influence of a high-fat diet and its combination with high-fructose intake on young normotensive rats, with focus on the modulatory effect of perivascular adipose tissue (PVAT) on the reactivity of isolated arteries. Six-week-old Wistar–Kyoto rats were treated for 8 weeks with a control diet (10% fat), a high-fat diet (HFD; 45% fat), or a combination of the HFD with a 10% solution of fructose. Contractile and relaxant responses of isolated rat arteries, with preserved and removed PVAT for selected vasoactive stimuli, were recorded isometrically by a force displacement transducer. The results demonstrated that, in young rats, eight weeks of the HFD might lead to body fat accumulation and early excitation of the cardiovascular sympathetic nervous system, as shown by increased heart rate and enhanced arterial contractile responses induced by endogenous noradrenaline released from perivascular sympathetic nerves. The addition of high-fructose intake deteriorated this state by impairment of arterial relaxation and resulted in mild elevation of systolic blood pressure; however, the increase in arterial neurogenic contractions was not detected. The diet-induced alterations in isolated arteries were observed only in the presence of PVAT, indicating that this structure is important in initiation of early vascular changes during the development of metabolic syndrome.


2018 ◽  
Vol 315 (6) ◽  
pp. R1085-R1095 ◽  
Author(s):  
Analia S. Loria ◽  
Frank T. Spradley ◽  
Ijeoma E. Obi ◽  
Bryan K. Becker ◽  
Carmen De Miguel ◽  
...  

Clinical studies have shown that obesity negatively impacts large arteries’ function. We reported that rats exposed to maternal separation (MatSep), a model of early life stress, display enhanced angiotensin II (ANG II)-induced vasoconstriction in aortic rings cleaned of perivascular adipose tissue (PVAT) under normal diet (ND) conditions. We hypothesized that exposure to MatSep promotes a greater loss of PVAT-mediated protective effects on vascular function and loss of blood pressure (BP) rhythm in rats fed a high-fat diet (HFD) when compared with controls. MatSep was performed in male Wistar-Kyoto rats from days 2 to 14 of life. Normally reared littermates served as controls. On ND, aortic rings from MatSep rats with PVAT removed showed increased ANG II-mediated vasoconstriction versus controls; however, rings from MatSep rats with intact PVAT displayed blunted constriction. This effect was exacerbated by an HFD in both groups; however, the anticontractile effect of PVAT was greater in MatSep rats. Acetylcholine-induced relaxation was similar in MatSep and control rats fed an ND, regardless of the presence of PVAT. HFD impaired aortic relaxation in rings without PVAT from MatSep rats, whereas the presence of PVAT improved relaxation in both groups. On an HFD, immunolocalization of vascular smooth muscle-derived ANG-(1–7) and PVAT-derived adiponectin abundances were increased in MatSep. In rats fed an HFD, 24-h BP and BP rhythms were similar between groups. In summary, MatSep enhanced the ability of PVAT to blunt the heightened ANG II-induced vasoconstriction and endothelial dysfunction in rats fed an HFD. This protective effect may be mediated via the upregulation of vasoprotective factors within the adipovascular axis.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Chorng-Kai Wen ◽  
Tzung-Yan Lee

Suppression of white adipose tissue inflammatory signaling may contribute to the pathogenesis of obesity-induced inflammatory response. However, the precise mechanism of efficacy of acupuncture related to adipose tissue remains poorly understood. In the present study we evaluated the anti-inflammatory activities of 10 Hz electroacupuncture (EA) which was applied at the acupoint Zusanli (ST36) for 20 min per day in high-fat diet- (HFD-) induced obesity model. Treatment lasted for one week. Obese rats treated with EA showed significantly reduced body weight compared with the rats in HFD group. EA decreased the number of F4/80 and CD11b-positive macrophages in epididymal adipose tissue. We found that 10 Hz EA given 7 days/week at ST36 acupoints significantly alleviated macrophage recruitment and then improved the obesity-associated factors of sterol regulatory element-binding protein-1 (SREBP-1) and target genes expression in rats with HFD. Adipose tissue inflammatory responses indicated by tumor necrosis factor-α(TNF-α), IL-6, monocyte chemotactic protein-1 (MCP-1), and CD68 mRNA expression were significantly reduced by EA in obese rats. Additionally, EA was found to significantly reduced serum levels of TNF-α, IL-6, and IL-1 in this model. These results indicated that EA improved adipose tissue inflammatory response in obese rats, at least partly, via attenuation of lipogenesis signaling.


2017 ◽  
Vol 174 (20) ◽  
pp. 3527-3541 ◽  
Author(s):  
Rafael Menezes da Costa ◽  
Rafael S Fais ◽  
Carlos R P Dechandt ◽  
Paulo Louzada-Junior ◽  
Luciane C Alberici ◽  
...  

2020 ◽  
Author(s):  
Hang-Hee Cho ◽  
Soo-Jung Lee ◽  
Sung-Ho Kim ◽  
Sun-Hee Jang ◽  
Chungkil Won ◽  
...  

Abstract Background: The aim of this study was to investigate the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 adipocyte-derived cells and anti-obesity properties in high fat diet (HFD)-induced obese rats. Methods: 3T3-L1 adipocytes and HFD-induced obese rats were treated with ATM, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Results: Cellular lipid contents in DMI (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, and peroxisome proliferator-activated receptor γ (PPARγ) expressions in 3T3-L1 cells. Moreover, treatment with ATM caused a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL), compared with DMI-stimulated adipocytes. In addition, phosphorylation levels of protein kinase B (Akt) and its downstream substrate, glycogen synthase kinase 3β (GSK3β), were significantly decreased by ATM treatment of 3T3-L1 adipocytes. Together, these results indicated that ATM caused inhibition of both adipocyte differentiation via suppression of the C/EBP family and PPARγ expressions and the Akt signaling pathway in 3T3-L1 adipocytes. In the present study, we further investigated anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with HFD demonstrated elevations in body weight gain, while the administration of ATM significantly reversed BW gains and adipose tissue weights in rats fed HFD. ATM supplementation also caused a decrease in the circulating triglyceride levels and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obesity in rats. Furthermore, epididymal fat exhibited larger adipocytes in the HFD group, whereas the ATM-treated group was significantly smaller than that of HFD group. These results strongly demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size. Conclusion: These finding demonstrated that ATM exerted anti-obesity effects through inhibition of adipocyte differentiation and adipogenesis, leading to a decrease in BW and fat tissue mass in HFD-induced obesity in rats.


2019 ◽  
Vol 62 ◽  
pp. 103519 ◽  
Author(s):  
Luis Jorge Coronado-Cáceres ◽  
Griselda Rabadán-Chávez ◽  
Lucía Quevedo-Corona ◽  
Blanca Hernández-Ledesma ◽  
Angel Miliar Garcia ◽  
...  

2005 ◽  
Vol 289 (5) ◽  
pp. H1807-H1813 ◽  
Author(s):  
Christine Barandier ◽  
Jean-Pierre Montani ◽  
Zhihong Yang

Adipocytes and perivascular adipose tissue are emerging as regulators of vascular function. The effects of adipocytes and perivascular adipose tissue on human smooth muscle cell (SMC) proliferation were investigated. Conditioned medium was prepared from cultured premature and differentiated 3T3-L1 adipocytes and from periaortic adipose tissue from young (3 mo) and old (24 mo) Wistar-Kyoto (WKY) rats, lean and obese Zucker rats (3 mo), and WKY rats fed normal chow or a high-fat diet for 3 mo. Conditioned medium from differentiated (but not premature) adipocytes stimulated SMC proliferation, which was abolished by charcoal and proteinase K treatment but was resistant to heat, trypsin, or phospholipase B (to hydrolyze lysophosphatidic acid). Further experiments demonstrated that the growth factor(s) are hydrosoluble and present in the fraction of molecular mass >100 kDa. Moreover, conditioned medium from periaortic adipose tissue stimulated SMC proliferation, which was significantly enhanced in aged rats and in rats fed a high-fat diet but not in obese Zucker rats deficient in functional leptin receptors. In conclusion, mature adipocytes release hydrosoluble protein growth factor(s) with a molecular mass >100 kDa for SMCs. Perivascular adipose tissue stimulates SMC proliferation, which is enhanced in aged WKY and in high-fat, diet-induced obesity but not in leptin receptor-deficient obese Zucker rats. These adipocyte-derived growth factor(s) and the effect of perivascular adipose tissue may be involved in vascular disease associated with aging and obesity.


2017 ◽  
Vol 174 (20) ◽  
pp. 3514-3526 ◽  
Author(s):  
Cristina M Sena ◽  
Ana Pereira ◽  
Rosa Fernandes ◽  
Liliana Letra ◽  
Raquel M Seiça

Sign in / Sign up

Export Citation Format

Share Document