Molecular implications of adenosine in obesity

Abstract

Adenosine has broad activities in organisms due to the existence of multiple receptors, the differential adenosine concentrations necessary to activate these receptors and the presence of proteins able to synthetize, degrade or transport this nucleoside. All adenosine receptors have been reported to be involved in glucose homeostasis, inflammation, adipogenesis, insulin resistance, and thermogenesis, indicating that adenosine could participate in the process of obesity. Since adenosine seems to be associated with several effects, it is plausible that adenosine participates in the initiation and development of obesity or may function to prevent it. Thus, the purpose of this review was to explore the involvement of adenosine in adipogenesis, insulin resistance and thermogenesis, with the aim of understanding how adenosine could be used to avoid, treat or improve the metabolic state of obesity. Treatment with specific agonists and/or antagonists of adenosine receptors could reverse the obesity state, since adenosine receptors normalizes several mechanisms involved in obesity, such as lipolysis, insulin sensitivity and thermogenesis. Furthermore, obesity is a preventable state, and the specific activation of adenosine receptors could aid in the prevention of obesity. Nevertheless, for the treatment of obesity and its consequences, more studies and therapeutic strategies in addition to adenosine are necessary.

Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT

“…Furthermore, the study subjects were all lean young men with only a small amount of subcutaneous WAT in the cervicothoracic area, which may also explain high variance in the WAT PET results. However, the most abundantly expressed adenosine receptors in WAT are the A 1 receptors, not A 2A receptors as in BAT [8, 30]. Studies with overweight subjects or PET scans of the abdominal area are needed to further assess the question of adenosine receptors in WAT.…”

Endoplasmic reticulum stress and development of insulin resistance in adipose, skeletal, liver, and foetoplacental tissue in diabesity

“…The increased incidence of T2DM and obesity worldwide shows a pattern of metabolic alterations that are not exclusive for obesity or T2DM, but a mix of clinical parameters, thus making every time more difficult to separate patients with obesity from those with T2DM only. Patients showing diabesity present with common characteristics that have been described for obesity or T2DM including endothelial and vascular, as well as skeletal muscle, adipose tissue, and liver dysfunction in response to vasoactive endogenous molecules such as insulin, adenosine, or endothelin-1 (Campia et al, 2014;Pardo et al, 2017;Silva et al, 2017).…”

Purinergic System Signaling in Metainflammation-Associated Osteoarthritis

“…A1R KO mice exhibit increased fat mass and body weight, and impaired glucose tolerance and insulin sensitivity ( 145 , 146 ). Contrary to A1R, the activation of A2BR, which is highly expressed in human primary pre-adipocytes ( 148 ), can inhibit both adipogenesis and lipogenesis in vitro ( 141 , 190 ). Moreover, in rodent models, the overexpression of A2BR seems to correlate with parameters of obesity, being upregulated in visceral adipose tissue of mice fed HFD ( 152 ).…”