Modulation of adenosinergic system as a therapeutic target for dysmetabolism

• Autor(a) principal: Leão, José Fernando Geraldes Malheiro Ponce de
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/163430
• topic: adenosinergic system; dysmetabolism; Ciências Médicas

Abstract Adenosine is involved in the regulation of white (WAT) and brown (BAT) adipose tissues and implicated in obesity and related diseases, however the specific contribution is still unknow. Moreover, the therapeutics for obesity and type 2 diabetes are scarce and not completely effective. Therefore, the present work aimed to investigate if dysmetabolic states are associated with alterations in adenosine receptors and adenosine metabolism in WAT and BAT and the mechanisms behind. Moreover, we explored the impact of chronic caffeine, an antagonist of adenosine receptors, treatment on these mechanisms. Three groups of Wistar rats were used: a control group that fed 25 weeks of standard diet, a HFHSu group that fed for 25 weeks a 60%-lipid rich diet plus 35% sucrose) in drinking water and a HFHSuCAF group submitted to HFHSu diet plus caffeine intake (1g/kg) in the last 11 weeks of diet. Rats were evaluated for weight gain, insulin sensitivity and glucose tolerance. WAT and BAT depots were collected and weighted. Ado was quantified in WAT and BAT by HPLC and Ado receptor levels and proteins involved in Ado metabolism analysed. We found that HFHSu animals exhibit insulin resistance and glucose intolerance, effects that were rescued and ameliorated by chronic caffeine treatment, respectively. HFHSu diet promoted an increase in weight gain and WAT depots without changing BAT amount, which was associated with decreased levels of adenosine content. These effects were rescued by chronic caffeine treatment. HFHSu diet decreased A2A and A2B levels in WAT in contrast with BAT where HFHSu diet promoted an increase in A2A levels and a decrease in A2B levels. All these effects were rescued by chronic caffeine administration. In both tissues no changes in A1 levels were observed. In WAT, HFHSu diet did not change ENT1 or CD73 levels but caffeine intake in HFHSu rats increased CD73 levels in comparison with HFHSu rats, and in BAT the diet produced an increase in ENT1 and CD73 levels. We can conclude that alterations in Ado receptor levels and Ado metabolism in adipose tissues are associated with metabolic dysfunction and that the modulation of Ado receptors with chronic caffeine intake can be useful to improve dysmetabolic states.