NLRP3 Inflammasome Signaling Platform as New Pharmacological Target for Metaflammation
Metaflammation is a metabolic inflammatory state characterized by chronic,
low grade inflammatory response initiated by excess nutrients in metabolic cells.
The inflammatory signaling conducted by the metabolic cell eventually causes activation
of specialized immune cells and leads to an unresolved inflammatory response within the tissue.
The high level of coordination of inflammatory and metabolic pathways is highlighted
by the overlapping biology and function of macrophages and adipocytes in obesity.
Preadipocytes under some conditions can exhibit phagocytic and antimicrobial properties
and appear to even be able to differentiate into macrophages in the right environment,
which suggests a potential immune role for preadipocytes.
Furthermore, macrophages and adipocytes co-localize in white adipose tissue in obesity.
Macrophages in adipose tissue are likely to contribute to the production of inflammatory
mediators either alone or in concert with adipocytes, which suggests a potentially important
influence of macrophages in promoting insulin resistance.
Besides macrophages, obesity is associated with aberrant expansion of other leukocytes
in adipose tissue that contribute to chronic inflammation. In particular,
the increased neutrophils lead to a rise of myeloperoxidase activity, a marker of neutrophil
infiltration, in the damaged tissue during inflammation.
Despite the role of meta-inflammation, in promoting metabolic diseases, including
obesity and insulin resistance, is well known,4 from a therapeutic perspective,
only limited experience is available regarding the inhibition of specific inflammatory
pathways activated by the metabolic, biochemical and haemodynamic derangements
known to exist in CMD.
Diabetes Res Open J. 2016; 3(1): e1-e3. doi: 10.17140/DROJ-3-e008