RESUMO
NLRP3 inflammasome has a key role in chronic low-grade metabolic inflammation, and its excessive activation may contribute to the beginning and progression of several diseases, including hepatic insulin resistance (hIR). Thus, this review aims to highlight the role of NLRP3 inflammasome and oxidative stress in the development of hIR and evidence related to phytochemical intervention in this context. In this review, we will address the hIR pathogenesis related to reactive oxygen species (ROS) production mechanisms, involving oxidized mitochondrial DNA (ox-mtDNA) and thioredoxin interacting protein (TXNIP) induction in the NLRP3 inflammasome activation. Moreover, we discuss the inhibitory effect of bioactive compounds on the insulin signaling pathway, and the role of microRNAs (miRNAs) in the phytochemical target mechanism in ameliorating hIR. Although most of the research in the field has been focused on evaluating the inhibitory effect of phytochemicals on the NLRP3 inflammasome pathway, further investigation and clinical studies are required to provide insights into the mechanisms of action, and, thus, encourage the use of these bioactive compounds as an additional therapeutic strategy to improve hIR and correlated conditions.
RESUMO
Severe food restriction (FR) is associated with blood pressure (BP) and cardiovascular dysfunction. The renin-angiotensin system (RAS) regulates BP and its dysregulation contributes to impaired cardiovascular function. Female Fischer rats were maintained on a control (CT) or severe FR (40% of CT) diet for 14 days. In response to severe FR, BP allostasis was achieved by up-regulating circulating Ang-[1-8] by 1.3-fold through increased angiotensin converting enzyme (ACE) activity and by increasing the expression of AT1Rs 1.7-fold in mesenteric vessels. Activation of the RAS countered the depressor effect of the severe plasma volume reduction (≥30%). The RAS, however, still underperformed as evidenced by reduced pressor responses to Ang-[1-8] even though AT1Rs were still responsive to the depressor effects of an AT1R antagonist. The aldosterone (ALDO) response was also inadequate as no changes in plasma ALDO were observed after the large fall in plasma volume. These findings have implications for individuals who have experienced a period(s) of severe FR (e.g., anorexia nervosa, dieters, natural disasters) and suggests increased activity of the RAS in order to achieve allostasis contributes to the cardiovascular dysfunction associated with inadequate food intake.
