Q2. What is the role of NLRP3 inflammasome in obesity?
The NLRP3 inflammasome seems to act as a sensor of metabolic danger signals that accumulate during obesity, including high levels of glucose [52], saturated free fatty acids [58, 59], lipid intermediates such as ceramides [56] and uric acid [51], and its activation results in IL-1β production and induction of numerous cytokines and chemokines.
Q3. What is the role of the immune system in the pathogenesis of type 2 diabetes?
A chronic low-grade inflammation and an activation of the immune system are observed in abdominal obesity and may have a role in the pathogenesis of obesity-related metabolic disorders [2-5].
Q4. What is the role of macrophages in obesity?
Although macrophages are the most abundant leukocyte population in expanding adipose tissue, the adaptive immune system may also contribute to obesity-induced inflammation.
Q5. What is the role of interleukin-1 in type 2 diabetes?
the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome.
Q6. What is the effect of weight loss on the adipose tissue?
weight loss induced by surgery [29] or diet and exercise [10] results in a reduction in the number of adipose tissue macrophages in parallel to the decreased expression of pro-inflammatory markers in both adipose tissue and plasma of obese individuals.
Q7. What is the role of fatty acids in causing adipocyte necrosis?
In the absence of additional nutrients supply, hypertrophy can also provoke adipocyte necrosis and the release of their cellular contents into the extracellular space triggering an inflammatory response.
Q8. What is the role of adipose tissue macrophages in metabolic syndrome?
In mouse models of obesity, an increased numbers of cytotoxic CD8+ effector cells is suspected to initiate the recruitment and activation of adipose tissue macrophages and promote pro-inflammatory cascades associated with insulin resistance [38, 40].
Q9. What is the role of inflammatory mediators in the liver?
pro-inflammatory mediators in the portal circulation, potentially produced by abdominal fat, might also initiate hepatic inflammation.
Q10. What is the role of TNF- in obesity-related insulin resistance?
Anti-TNFαTNFα was the first pro-inflammatory cytokine implicated in pathogenesis of obesity-related insulin resistance and T2DM [28].
Q11. What was the effect of weight loss on insulin sensitivity?
improvement in insulin sensitivity induced by weight loss was accompanied by a decrease in the expression of pro-inflammatory genes [28, 29].
Q12. What is the role of IL-1 in the progression of T2DM?
3.1. IL-1β and NLRP3 inflammasomeIL-1β, one of the major pro-inflammatory cytokine produced by macrophages, has been shown to be a key contributor to the pathogenesis of T2DM.
Q13. What is the role of TNF- in obesity-related metabolic disorders?
A local inflammation is also observed in the liver and skeletal muscle but its role in obesity-related metabolic disorders still needs to be determined.
Q14. What is the effect of IL-1 blocking on glucose control in diabetic patients?
Although the short duration of these studies does not provide definitive conclusions, data suggests that IL-1β blocking activity enhances glucose control in diabetic patients by improving the β-cell function and may even allow a partial generation these cells.
Q15. What is the role of regulatory T cells in preventing obesity?
These data suggest that regulatory T cells may repress adipose tissue inflammation and play a role in providing protection against insulin resistance-induced inflammation linked to obesity [33, 37].
Q16. What is the role of IL-1 in the pathogenesis of T2DM?
4.1. Anti-IL-1βConsidering the central role of NLRP3 inflammasome and IL-1β in the pathogenesis of T2DM, it is not surprising that the blockade of IL-1β activity has shown improvement in glucose control in prediabetic or T2DM populations.
Q17. What are the biomarkers associated with obesity-related metabolic syndrome?
The authors will also examine the biological, tissular and cellular inflammatory markers associated with obesity-related metabolic disorders that may predict the development of T2DM.