Constitutive P2Y2 receptor activity regulates basal lipolysis in human adipocytes

Ali, Seema; Turner, Jeremy; Fountain, Samuel J.

doi:10.1242/jcs.221994

Cited by 19 publications

(23 citation statements)

References 63 publications

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“…In accordance with recent studies, AR-C118925 was chosen for blockage of the upregulated P 2 Y 2 Rs. 8,18,19,36 The results of the current study showed attenuation of bilateral hypersensitivity after AR-C118925 was administered ipsilateral to the inflammation. This suggests that the analgesic effect of AR-C118925 on ipsilateral MM hypersensitivity may be mediated by its effect on P 2 Y 2 Rs.…”

Section: Controlsupporting

confidence: 51%

“…According to a recent study, the constitutive P 2 Y 2 Rs activity produces intracellular Ca 2+ tone and suppresses basal lipolysis via an adenylate cyclase-dependent mechanism in human adipocytes. 18 Muoboghare et al have suggested that UTP acts via P 2 Y 2 Rs to mobilise Ca 2+ in human endothelial cells. 19 Recent studies have investigated the role of P 2 Y 2 Rs in pain mechanisms, but their exact function remains unclear, especially in the fields of orofacial pain and TMD.…”

Section: Introductionmentioning

confidence: 99%

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P2Y2 Receptors Mediate Masseter Muscle Mechanical Hypersensitivity in Rats

Knežević

Vukman

Uhač

et al. 2020

JPR

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Purpose: P 2 Y 2 receptors (P 2 Y 2 Rs) are among the various receptors that play an important role in nociception. The goal of this research was to investigate possible P 2 Y 2 R expression changes in the trigeminal ganglion (TRG) in bilateral masseter muscle (MM) hypersensitivity following unilateral MM inflammation. The impact of unilateral intramasseteric administration of P 2 Y 2 R antagonist on bilateral MM hypersensitivity was also explored. Materials and Methods: Bilateral MM hypersensitivity was provoked by unilateral intramasseteric injection of complete Freund's adjuvant (CFA). The head withdrawal threshold (HWT) was assessed bilaterally 4 days later. Bilateral TRG and MM isolation were followed, and quantitative real-time polymerase chain reaction (qRT-PCR) and histopathological analysis were carried out on these tissues, respectively. The involvement of P 2 Y 2 Rs in nocifensive behavior was evaluated by administering two doses of P 2 Y 2 R antagonist AR-C118925 (0.2 or 1 mg/100 μL) in inflamed MM 4 days post-CFA administration. Bilateral HWT was assessed at different time points following antagonist injection. Results: qRT-PCR analysis demonstrated P 2 Y 2 R up-regulation in TRG ipsilateral to the site of CFA administration. Compared to the controls, both doses of AR-C118925 injected ipsilateral to the TRG increased the bilateral HWT at 30, 60, 90, and 120 minutes after antagonist administration. Conclusion: The findings suggest that P 2 Y 2 Rs may affect MM inflammatory hypersensitivity owing to its up-regulation in the TRG in MM inflammatory pain states.

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Section: Controlsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

P2Y2 Receptors Mediate Masseter Muscle Mechanical Hypersensitivity in Rats

Knežević

Vukman

Uhač

et al. 2020

JPR

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“…Recently it has been reported that constitutive P2Y 2 receptor activity suppresses basal lipolysis in human adipocytes. Ali et al (58) showed that pharmacological antagonism or knockdown of P2Y 2 receptor increases intracellular cAMP levels and enhances basal lipolysis. They also observed that acute enhancement of basal lipolysis following P2Y 2 receptor antagonism alters the profile of secreted adipokines leading to long-term adaptive decrease in lipolysis.…”

Section: Discussionmentioning

confidence: 99%

“…They also observed that acute enhancement of basal lipolysis following P2Y 2 receptor antagonism alters the profile of secreted adipokines leading to long-term adaptive decrease in lipolysis. Based on their findings, Ali et al (58) concluded that basal lipolysis and adipokine secretion are controlled by autocrine purinergic signaling in human adipocytes. Our above observations on the alterations in plasma lipids and adipokines in P2Y 2 receptor KO mice fed high-fat diet are consistent with this report.…”

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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“…Perivascular adipose tissue (PVAT), a layer of fatty tissue which surrounds blood vessels, is now known to release a variety of adipokines and other factors which regulate vascular tone [87,88]. Adipose tissue expresses P2 receptors which can be activated by ATP released from perivascular sympathetic nerves to regulate lipolysis [89][90][91], and there is evidence for constitutive release of nucleotides from adipocytes in regulation of lipolysis [92]. In obesity, the increase in adipocyte area and mass leads to hypoxia [88].…”

Section: Roles Of Purines In the Cardiovascular Systemmentioning

confidence: 99%

Purinergic signalling in the cardiovascular system—a tribute to Geoffrey Burnstock

Ralevic

2020

Purinergic Signalling

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Geoffrey Burnstock made groundbreaking discoveries on the physiological roles of purinergic receptors and led on P2 purinergic receptor classification. His knowledge, vision and leadership inspired and influenced the international scientific community. I had the privilege of spending over 10 years (from 1985) with Geoff at the Department of Anatomy and Developmental Biology, initially as a PhD student and then as a postdoctoral research fellow. I regarded him with enormous admiration and affection. This review on purinergic signalling in the cardiovascular system is a tribute to Geoff. It includes some personal recollections of Geoff.

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Constitutive P2Y2 receptor activity regulates basal lipolysis in human adipocytes

Cited by 19 publications

References 63 publications

<p>P<sub>2</sub>Y<sub>2</sub> Receptors Mediate Masseter Muscle Mechanical Hypersensitivity in Rats</p>

<p>P<sub>2</sub>Y<sub>2</sub> Receptors Mediate Masseter Muscle Mechanical Hypersensitivity in Rats</p>

P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity

Purinergic signalling in the cardiovascular system—a tribute to Geoffrey Burnstock

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