AT expression of IL-18 is increased in obesity but not affected by weight loss, indicating that changes in plasma IL-18 are related to insulin resistance rather than changes in obesity per se.
We demonstrated that obesity (P < 0.01), obesity-associated T2D (P < 0.01) and NAFLD (P < 0.05) increased the expression of different components of the inflammasome as well as the expression and release of IL-1β and IL-18 in AT.
CD14 and IL-18 were overexpressed in omental adipose tissue compared with the subcutaneous depot, irrespective of the subject's obesity or diabetes status.
Interleukin-18 (IL-18) improves the insulin resistance associated with obesity, but the relationship between IL-18 and glucose metabolism in sepsis was unclear.
This finding supports the concepts that adipocytes behave as primitive immune cells and that IL-18 may mediate some of the detrimental complications of obesity such as cardiovascular disease and type 2 diabetes.
Therefore, variation within IL18, previously shown to be associated with lower IL18 levels, is influencing measures of obesity both in men with type 2 diabetes mellitus and those with advanced coronary heart disease.
The hypothesis that obesity is associated with increased adipose tissue (AT) interleukin (IL)-18 mRNA expression and that AT IL-18 mRNA expression is related to insulin resistance was tested.
The evolutive advantages of increased inflammatory responses, hypersecretion of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-18], or decreased anti-inflammatory molecules (adiponectin, certain TNF-alpha isoforms, soluble CD14, etc.), would lead in westernized countries to chronic inflammation conditions, such as obesity and type 2 diabetes, resulting in cardiovascular disease.
We further revealed that activated nod-like receptor protein 3 (NLRP3) inflammasome and its downstream products, i.e., IL-1 family members such as IL-1β and IL-18 were upregulated in the PVAT of obese mini pigs; PVAT dysfunction was also demonstrated in preadipocytes treated with palmitic acid.
The pyrogenic property being the first activity described, members of the interleukin-1 superfamily (IL-1α, IL-1β, IL-18, and the newest members: IL-33, IL-36, IL-37, and IL-38) are now known to be involved in several inflammatory diseases such as obesity, atherosclerosis, cancer, viral and parasite infections, and auto-inflammatory syndromes as well as liver diseases.
By their capacity to express inflammatory-related factors, and in particular the proinflammatory cytokine IL-18 in OAT, mesothelial cells appear as a new player in the process of low-grade inflammation associated with obesity.
IL-18 mediates diet-induced cardiac dysfunction, independent of food intake and obesity, thus highlighting a disconnect between the metabolic and cardiac effects of IL-18.