Pitfalls and challenges of the purinergic signaling cascade in obesity.

Autor: de Oliveira M; São Paulo State University (UNESP), Botucatu Medical School, District of Rubião Jr, s/n, 18618-000, Botucatu, São Paulo, Brazil., Mathias LS; São Paulo State University (UNESP), Botucatu Medical School, District of Rubião Jr, s/n, 18618-000, Botucatu, São Paulo, Brazil., de Sibio MT; São Paulo State University (UNESP), Botucatu Medical School, District of Rubião Jr, s/n, 18618-000, Botucatu, São Paulo, Brazil., Noronha-Matos JB; Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP); Center for Drug Discovery and Innovative Medicines (MedInUP), Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP)., Costa MA; Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP); Center for Drug Discovery and Innovative Medicines (MedInUP), Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP); Departamento de Química, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP)., Nogueira CR; São Paulo State University (UNESP), Botucatu Medical School, District of Rubião Jr, s/n, 18618-000, Botucatu, São Paulo, Brazil., Correia-de-Sá P; Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP); Center for Drug Discovery and Innovative Medicines (MedInUP), Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP). Electronic address: farmacol@icbas.up.pt.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2020 Dec; Vol. 182, pp. 114214. Date of Electronic Publication: 2020 Sep 06.
DOI: 10.1016/j.bcp.2020.114214
Abstrakt: Obesity is a worldwide health problem which have reached pandemic proportions, now also including low and middle-income countries. Excessive or abnormal fat deposition in the abdomen especially in the visceral compartment is tightly associated with a high metabolic risk for arterial hypertension, type II diabetes, cardiovascular diseases, musculoskeletal disorders (especially articular degeneration) and some cancers. Contrariwise, accumulation of fat in the subcutaneous compartment has been associated with a neutral metabolic impact, favoring a lower risk of insulin resistance. Obesity results more often from an avoidable imbalance between food consumption and energy expenditure. There are several recommended strategies for dealing with obesity, including pharmacological therapies, but their success remains incomplete and may not compensate the associated adverse effects. Purinergic signaling operated by ATP and its metabolite, adenosine, has attracted increasing attention in obesity. The extracellular levels of purines often reflect the energy status of a given cell population. Adenine nucleotides and nucleosides fine tuning control adipogenesis and mature adipocytes function via the activation of P2 and P1 purinoceptors, respectively. These features make the purinergic signaling cascade a putative target for therapeutic intervention in obesity and related metabolic syndromes. There are, however, gaps in our knowledge regarding the role of purines in adipocyte precursors differentiation and mature adipocytes functions, as well as their impact among distinct adipose tissue deposits (e.g. white vs. brown, visceral vs. subcutaneous), which warrants further investigations before translation to clinical trials can be made.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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