Considering the fact that obesity is an inflammatory condition that is definitely also related with elevated TLR2 expression in adipose tis sue, adipocyte TLR2 could certainly mediate part of the inflammatory environment that characterizes obesity. Thus, targeting TLR2 may well contribute to prevention of obesity induced inflammation. Given that obes ity can also be associated with elevated fatty acid levels, the induction of TLR2 expression by both DHA and EPA indi vidually and additively with peptidoglycan along with the addi tive induction of TLR2 by each linoleic acid and peptidoglycan suggests that fatty acids may be partly accountable for the upregulation of TLR2 in obesity. This also suggests that regulation of TLR2 mediated cellular responses may perhaps be fatty acid certain.
Elevated fatty acid concentrations in obesity may amplify the inflammatory cascade which is induced by but unidentified endogenous ligands for TLR2. Even though omega three fatty acids, EPA and DHA at moderate levels are recognized to exert anti inflam matory effects, elevated levels of those fatty acids in circu lation has been demonstrated to result in enhanced our website inflammation characterized by improved macrophage infiltration into adipose tissue. Thus, the levels of those fatty acids as utilized within this experiment mimic more closely the hyperlipidemic condition that is definitely charac terized by elevated fatty acid concentrations. The additiv ity of effects of fatty acids and peptidoglycan around the induction of TLR expression suggests that beneath the hyperlipidemic conditions of obesity fatty acids and lig ands of TLRs could co operate to amplify the inflammatory state by further rising the expression of TLRs.
This may perhaps be a mechanism to stop desensitization for the effects of TLR ligands in obesity. Interestingly, whereas inhibition of p44 42 MAPK and c JNK suppressed peptidoglycan induction of IL6, it ampli fies the induction of TLR2 mRNA by peptidoglycan. This observation agrees with the upreguation of TLR2 mRNA by p44 42 MAPK inhibition with PD 98059 in RAW PI103 264. 7 macrophages. Moreover, it indicates that these kinase pathways, although they mediate positively the induction of IL6 by peptidoglycan, they might also be involved inside a damaging feedback mechanism to stop an upregulation of TLR2 for the duration of inflammation, maybe to stop on overzealous inflammatory reaction. The downregulation of expression of each adiponectin receptors by peptidoglycan parallels the reduction of sol uble adiponectin receptor expression just after the administra tion of LPS to human subjects and suggests that TLR2 activation in obesity could partly be responsible for the downregulation of adiponectin receptor expression in adipose tissue in obesity. Thus, this may possibly impli cate TLR2 in phenomenon of obesity induced adiponec tin resistance.