de Oliveira Miriane, Mathias Lucas Solla, de Sibio Maria Teresa, Noronha-Matos José Bernardo, Costa Maria Adelina, Nogueira Célia Regina, Correia-de-Sá Paulo
São Paulo State University (UNESP), Botucatu Medical School, District of Rubião Jr, s/n, 18618-000, Botucatu, São Paulo, Brazil.
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).
Biochem Pharmacol. 2020 Dec;182:114214. doi: 10.1016/j.bcp.2020.114214. Epub 2020 Sep 6.
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.
肥胖是一个全球性的健康问题，已达到大流行程度，现在低收入和中等收入国家也未能幸免。腹部尤其是内脏部位过多或异常的脂肪沉积与动脉高血压、II型糖尿病、心血管疾病、肌肉骨骼疾病（尤其是关节退变）和某些癌症的高代谢风险密切相关。相反，皮下部位的脂肪堆积与中性代谢影响有关，有利于降低胰岛素抵抗风险。肥胖更多是由食物摄入与能量消耗之间可避免的失衡导致的。处理肥胖有几种推荐策略，包括药物治疗，但其成功率仍不高，且可能无法抵消相关的不良反应。由ATP及其代谢产物腺苷介导的嘌呤能信号传导在肥胖领域受到越来越多的关注。嘌呤的细胞外水平通常反映特定细胞群体的能量状态。腺嘌呤核苷酸和核苷分别通过激活P2和P1嘌呤受体来微调脂肪生成和成熟脂肪细胞的功能。这些特性使嘌呤能信号级联成为肥胖及相关代谢综合征治疗干预的潜在靶点。然而，我们对嘌呤在脂肪细胞前体分化和成熟脂肪细胞功能中的作用，以及它们在不同脂肪组织沉积（如白色与棕色、内脏与皮下）中的影响了解尚存在空白，在转化为临床试验之前，这需要进一步研究。
