Elevated concentrations of plasma adenosine in obese children

Escudero, Andrea; Carreño, Barbara; Retamal, Nicole; Celis, Cristian; Castro, Luis Antônio Suíta de; Aguayo, Claudio; Acurio, Jesenia; Escudero, Carlos

doi:10.1002/biof.1039

Cited by 9 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results agree with previous reports in obese adults showing high adenosine levels in adipose tissue homogenates [17]. We also found high plasma adenosine levels in obese children [18]. Because adipocytes [17,33] and the placenta [34] have all the metabolic machinery necessary for synthesizing adenosine, it is not surprising that overweight/obese pregnant women exhibit high adenosine levels.…”

Section: Adenosine In Obesitysupporting

confidence: 93%

“…The gestational age was defined as the period of time from the first day of the mother's last menstrual period and the delivery date; this age was confirmed with a first trimester ultrasound. Body mass index (BMI = kg/m 2 ) was determined as described elsewhere [18]. Women were classified as lean (18.5-24.9 kg/m 2 ) and overweight/obese (>25 kg/m 2 ) based on BMI.…”

Section: Patientsmentioning

confidence: 99%

“…In this regard, no reports concerning plasma adenosine levels in overweight/obese pregnant women have been published. But, high concentrations of this molecule were found in the homogenates of adipose tissue obtained from obese adults [17] or in plasma from obese children [18].…”

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

High plasma adenosine levels in overweight/obese pregnant women

Badillo

Salgado

Bravo

et al. 2017

Purinergic Signalling

Self Cite

View full text Add to dashboard Cite

We aim to investigate whether overweight/obese pregnant women have elevated plasma levels of adenosine associated with increased consumption of high-calorie food. Sixty women were included. They were divided into lean (n = 23 and n = 12) or overweight/obese (n = 7 and n = 18) non-pregnant and pregnant women, respectively. Clinical records and maternal blood samples were collected after informed consent. A self-reported dietary questionnaire was also completed. Plasma adenosine levels were determined with high-performance liquid chromatography. Biochemical parameters, including glucose, total protein, and lipid profile, were determined using standard colorimetric assays. Adenosine levels were higher in pregnant women than in non-pregnant women (18.7 ± 1.6 vs 10.8 ± 1.3 nM/μg protein, respectively, p < 0.0001). Overweight/obese pregnant women (21.9 ± 2.5 nM/μg protein) exhibited higher adenosine levels than lean pregnant (14.5 ± 1.0 nM/μg protein, p = 0.04) or non-pregnant women (11.7 ± 1.5 nM/μg protein, p = 0.0005). Also, pregnant women with elevated weight gain exhibited higher (26.2 ± 3.7 nM/μg protein) adenosine levels than those with adequate weight gain (14.9 ± 1.4 nM/μg protein, p = 0.03). These differences were not statistically significant compared with those of pregnant women with reduced weight gain (17.4 ± 2.1 nM/μg protein, p = 0.053). Body mass index and adenosine only in pregnant women were positively correlated (r = 0.39, p = 0.02). While, polyunsaturated fatty acid (PUFA) consumption was negatively correlated with plasma adenosine levels only in non-pregnant women (r = -0.33, p = 0.03). Pregnancy is associated with high plasma adenosine levels, which are further elevated in pregnant women who are overweight/obese. High PUFA intake might reduce plasma adenosine levels in non-pregnant women.

show abstract

Section: Adenosine In Obesitysupporting

confidence: 93%

Section: Patientsmentioning

confidence: 99%

See 1 more Smart Citation

High plasma adenosine levels in overweight/obese pregnant women

Badillo

Salgado

Bravo

et al. 2017

Purinergic Signalling

Self Cite

View full text Add to dashboard Cite

show abstract

“…Decreased expression of adenosine transporters and high levels of adenosine, which competitively may inhibit cellular uptake of GS-441524, have the potential to reduce the effectiveness of this drug in the treatment of COVID-19. Cellular uptake of GS-441524 in patients with COVID-19 may also be reduced by comorbidities associated with increased extracellular adenosine levels, such as severe cardiovascular disease [ 63 ], obesity [ 64 ], and cancer [ 48 ] in addition to comorbidities or complications of COVID-19 requiring treatment with agents that increase extracellular adenosine levels. Similarly, uptake of GS-441524 after pulmonary delivery, a recently proposed treatment of COVID-19 [ 11 ], may be reduced by high levels of adenosine in the bronchoalveolar epithelial lining fluid.…”

Section: Extracellular Adenosine Levelsmentioning

confidence: 99%

Cellular Uptake and Intracellular Phosphorylation of GS-441524: Implications for Its Effectiveness against COVID-19

Rasmussen

Jürgens

Thomsen

et al. 2021

Viruses

View full text Add to dashboard Cite

GS-441524 is an adenosine analog and the parent nucleoside of the prodrug remdesivir, which has received emergency approval for treatment of COVID-19. Recently, GS-441524 has been proposed to be effective in the treatment of COVID-19, perhaps even being superior to remdesivir for treatment of this disease. Evaluation of the clinical effectiveness of GS-441524 requires understanding of its uptake and intracellular conversion to GS-441524 triphosphate, the active antiviral substance. We here discuss the potential impact of these pharmacokinetic steps of GS-441524 on the formation of its active antiviral substance and effectiveness for treatment of COVID-19. Available protein expression data suggest that several adenosine transporters are expressed at only low levels in the epithelial cells lining the alveoli in the lungs, i.e., the alveolar cells or pneumocytes from healthy lungs. This may limit uptake of GS-441524. Importantly, cellular uptake of GS-441524 may be reduced during hypoxia and inflammation due to decreased expression of adenosine transporters. Similarly, hypoxia and inflammation may lead to reduced expression of adenosine kinase, which is believed to convert GS-441524 to GS-441524 monophosphate, the perceived rate-limiting step in the intracellular formation of GS-441524 triphosphate. Moreover, increases in extracellular and intracellular levels of adenosine, which may occur during critical illnesses, has the potential to competitively decrease cellular uptake and phosphorylation of GS-441524. Taken together, tissue hypoxia and severe inflammation in COVID-19 may lead to reduced uptake and phosphorylation of GS-441524 with lowered therapeutic effectiveness as a potential outcome. Hypoxia may be particularly critical to the ability of GS-441524 to eliminate SARS-CoV-2 from tissues with low basal expression of adenosine transporters, such as alveolar cells. This knowledge may also be relevant to treatments with other antiviral adenosine analogs and anticancer adenosine analogs as well.

show abstract

“…A review about adenosine and adipogenesis is available [121]. High plasma levels of adenosine were found in children with obesity [122] and in overweight pregnant women [123]. Non-alcoholic fatty liver disease is an obesity-related condition.…”

Section: Regulatory Role Of Adenosine and P1 Receptors In Obesitymentioning

confidence: 99%

The involvement of purinergic signalling in obesity

Burnstock

Gentile

2018

Purinergic Signalling

View full text Add to dashboard Cite

Obesity is a growing worldwide health problem, with an alarming increasing prevalence in developed countries, caused by a dysregulation of energy balance. Currently, no wholly successful pharmacological treatments are available for obesity and related adverse consequences. In recent years, hints obtained from several experimental animal models support the notion that purinergic signalling, 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. This review has drawn together, for the first time, the evidence for a promising, much needed novel therapeutic purinergic signalling approach for the treatment of obesity with a ‘proof of concept’ that hopefully could lead to further investigations and clinical trials for the management of obesity.

show abstract

Elevated concentrations of plasma adenosine in obese children

Cited by 9 publications

References 42 publications

High plasma adenosine levels in overweight/obese pregnant women

High plasma adenosine levels in overweight/obese pregnant women

Cellular Uptake and Intracellular Phosphorylation of GS-441524: Implications for Its Effectiveness against COVID-19

The involvement of purinergic signalling in obesity

Contact Info

Product

Resources

About