The involvement of purinergic signalling in obesity

Burnstock, Geoffrey; Gentile, Daniela

doi:10.1007/s11302-018-9605-8

Cited by 36 publications

(31 citation statements)

References 129 publications

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“…Finally, a recent review of the involvement of purinergic signaling in obesity by Burnstock and Gentile (60) states that currently, no wholly successful pharmacological treatments are available for obesity and related adverse consequences. It also adds that in recent years, hints obtained from several experimental animal models support the notion that purinergic signaling, acting through ATP-gated ion channels (P2X), G protein-coupled receptors (P2Y), and adenosine receptors (P1), is involved in obesity, both at peripheral and central levels.…”

Section: Discussionmentioning

confidence: 99%

P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity

et al. 2020

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P2Y 2 , a G protein-coupled receptor (R), is expressed in all organs involved in the development of obesity and insulin resistance. To explore the role of it in diet-induced obesity, we fed male P2Y 2-R whole body knockout (KO) and wild type (WT) mice (B6D2 genetic background) with regular diet (CNT; 10% calories as fat) or high-fat diet (HFD; 60% calories as fat) with free access to food and water for 16 weeks, and euthanized them. Adjusted for body weights (BW), KO mice consumed modestly, but significantly more HFD vs. WT mice, and excreted well-formed feces with no taint of fat or oil. Starting from the 2nd week, HFD-WT mice displayed significantly higher BW with terminal mean difference of 22% vs. HFD-KO mice. Terminal weights of white adipose tissue (WAT) were significantly lower in the HFD-KO vs. HFD-WT mice. The expression of P2Y 2-R mRNA in WAT was increased by 2-fold in HFD-fed WT mice. Serum insulin, leptin and adiponectin levels were significantly elevated in the HFD-WT mice, but not in the HFD-KO mice. When induced in vitro, preadipocytes derived from KO mice fed regular diet did not differentiate and mature as robustly as those from the WT mice, as assessed by cellular expansion and accumulation of lipid droplets. Blockade of P2Y 2-R by AR-C118925 in preadipocytes derived from WT mice prevented differentiation and maturation. Under basal conditions, KO mice had significantly higher serum triglycerides and showed slightly impaired lipid tolerance as compared to the WT mice. HFD-fed KO mice had significantly better glucose tolerance (GTT) as compared to HFD-fed WT mice. Whole body insulin sensitivity and mRNA expression of insulin receptor, IRS-1 and GLUT4 in WAT was significantly higher in HFD-fed KO mice vs. HFD-fed WT mice. On the contrary, the expression of pro-inflammatory molecules MCP-1, CCR2, CD68, and F4/80 were significantly higher in the WAT of HFD-fed WT vs. HFD-fed KO mice. These data suggest that P2Y 2-R plays a significant role in the development of diet-induced obesity by promoting adipogenesis and inflammation, and altering the production of adipokines and lipids and their metabolism in adipose tissue, and thereby facilitates HFD-induced insulin resistance.

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Section: Discussionmentioning

confidence: 99%

P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity

et al. 2020

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“…Literature suggests that blueberries consumption has been associated with amelioration of obesity as well as diminution of obesity-related pro-inflammatory molecules (Badillo et al, 2017;Burnstock & Gentile, 2018;Cáceres-Medina et al, 2015;Margalef et al, 2017;Noratto et al, 2016;Oviedo-Solís, Cornejo-Manzo, & Murillo-Ortiz, 2018;Pandolfi et al, 2015;Wyckoff, Evans, Manasse, Butryn, & Forman, 2017). Thus, we included blueberries as beneficial health-promoting food in hypocaloric diet as suggested by others (Wu, Yang, et al, 2018;Zhang, Ma, Luo, & Li, 2018).…”

Section: Hypocaloric Diet Including Blueberries Intakementioning

confidence: 99%

Blueberry intake included in hypocaloric diet decreases weight, glucose, cholesterol, triglycerides and adenosine levels in obese subjects

Higuera-Hernández

Reyes-Cuapio

Gutiérrez-Mendoza

et al. 2019

Journal of Functional Foods

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Obesity is a disease characterized by an excessive accumulation of fat in the body and it has been linked the enhancement of inflammation-related endogenous molecules, such as adenosine (AD). Since blueberries may induce anti-obesity effects, we tested the hypothesis that blueberries consumption contained in hypocaloric diet would decrease weight, BMI as well as glucose, cholesterol, triglycerides and AD levels in obese subjects. The baseline conditions of obesity-related variables were collected for all subjects prior the implementation of blueberries intake. Later, participants received a hypocaloric diet that included the consumption of blueberries (50 g/ day) during 30 days. We found that male obese subjects that consumed blueberries showed a decrease in weight, glucose, cholesterol, triglycerides and AD whereas female obese subjects that ate blueberries in hypocaloric diet showed no differences in weight, BMI, glucose and triglycerides but displayed a diminution in cholesterol and AD levels. Data suggest that intake of blueberries seems to decrease some of the obese-linked parameters in male or female subjects. Importantly, blueberry consumption decreased the inflammation-related compound AD in both sexes.

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“…Therefore, apparently discordant findings may result from the discrepancies between genetic deletion of the P2Y 6 receptor and pharmacological inhibition. Beyond that, the P2Y 6 receptor is widely expressed on the cell surface of intimal endothelial cells [14,50], medial VSMCs [50,51], macrophages or T cells [52][53][54], and perivascular adipocytes [55], which all take part in AAA formation. There are still evidences demonstrating that activation of P2Y 6 could exert an anti-inflammation role in different kinds of cells [46,47], such as T cells.…”

Section: Discussionmentioning

confidence: 99%

The Role of a Selective P2Y₆ Receptor Antagonist, MRS2578, on the Formation of Angiotensin II-Induced Abdominal Aortic Aneurysms

Zhang

Xiang

et al. 2020

BioMed Research International

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Objective. The P2Y 6 receptor has been shown to be involved in many cardiovascular diseases, including hypertension and atherosclerosis. The study is aimed at exploring the role of the P2Y 6 receptor in Ang II-induced abdominal aortic aneurysm (AAA) formation in apolipoprotein E-deficient (apoE -/-) mice by using its selective antagonist. Methods. Male apoE -/mice were fed with high-fat diet and infused with angiotensin (Ang) II (1000 ng/kg/min) for 4 weeks to induce AAA or saline as controls. Mice were divided into four groups: normal saline (NS, placebo control) group (n = 8), Ang II+vehicle (Ang II) group (n = 14), Ang II-low dose MRS2578 (Ang II+MRS-16 mg) group (n = 14), and Ang II-high dose MRS2578 (Ang II+MRS-32 mg) group (n = 14). Daily intraperitoneal injection with vehicle or MRS2578 was pretreated one week before Ang II infusion. On postoperative day 10, aorta imaging of each group was taken by ultrasonography. After 4 weeks of Ang II infusion, the excised aortas were processed for diameter measurement and quantification of aneurysm severity and tissue characteristics; the blood samples were collected for measurement of the lipid profile and levels of cytokines. Verhoeff's Van Gieson (EVG) staining and immunochemistry staining were performed to evaluate disruption of the extracellular matrix (ECM) and infiltration of macrophages. Expression and activity of matrix metalloproteinases (MMPs) was measured by gelatin zymography. Results. Treatment with MRS2578 made no significant difference in AAA formation, and maximal aortic diameter yet caused higher AAA rupture-induced mortality from 7% (Ang II) to 21.4% (Ang II+MRS-16 mg) or 42.9% (Ang II+MRS-32 mg), respectively (p < 0:05). Consistently, the severity of aneurysm tended to be more deteriorated in MRS2578-treated groups, especially the high-dosage group. The ratios of type III and IV aneurysm were much higher in the MRS2578-coadministered groups (p < 0:05). Furthermore, histological analyses showed that administration of MRS2578 significantly increased infiltration of macrophages, expression of monocyte chemotactic protein 1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1), and activities of MMP-2 and MMP-9 followed by aggravating degradation elastin in vivo (p < 0:05). However, the multiple effects of MRS2578 on the development of AAA are independent of changes in systolic blood pressure and lipid profiles. Conclusions. The present study demonstrated that administration of MRS2578 exacerbated the progression and rupture of experimental AAA through promoting proinflammatory response and MMP expression and activity, which indicated a crucial role of the P2Y 6 receptor in AAA development. Clinical Relevance. Purinergic P2Y receptors have attracted much attention since the P2Y 12 receptor antagonist had been successfully applied in clinical practice. Elucidating the underlying mechanisms of AAA and exploring potential therapeutic strategies are essential to prevent its progression and reduce the mortality rate.

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The involvement of purinergic signalling in obesity

Cited by 36 publications

References 129 publications

P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity

P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity

Blueberry intake included in hypocaloric diet decreases weight, glucose, cholesterol, triglycerides and adenosine levels in obese subjects

The Role of a Selective P2Y₆ Receptor Antagonist, MRS2578, on the Formation of Angiotensin II-Induced Abdominal Aortic Aneurysms

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The involvement of purinergic signalling in obesity

Cited by 36 publications

References 129 publications

P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity

P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity

Blueberry intake included in hypocaloric diet decreases weight, glucose, cholesterol, triglycerides and adenosine levels in obese subjects

The Role of a Selective P2Y6 Receptor Antagonist, MRS2578, on the Formation of Angiotensin II-Induced Abdominal Aortic Aneurysms

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The Role of a Selective P2Y₆ Receptor Antagonist, MRS2578, on the Formation of Angiotensin II-Induced Abdominal Aortic Aneurysms