Understanding and Modulating the Toll Like Receptors (TLRs) and NOD Like Receptors (NLRs) Cross Talk in Type 2 Diabetes
Bhumika Prajapati, Prasant Kumar Jena, Parth Rajput, Kaveri Purandhar and Sriram Seshadri
Pages 190-200 (11)
Obesity and Type 2 diabetes are leading health problems which are characterized by low-grade inflammation
with an increase in inflammatory cytokines along with the change in the gut microbiota population. Toll like Receptors
(TLRs) and NOD like Receptors (NLRs) are very prominent pathogen recognition receptors, which play a significant role
in the innate immune system. Both TLRs and NLRs pathways are mediated through different adaptor proteins; commonly
found to activate the NF-kB, which induces the expression of proinflammatory cytokines. It has been suggested that TLRs
and NLRs have a significant role in the pathogenesis of inflammation mediated insulin resistance, which further develops
metabolic complications. TLRs mediated mechanism for insulin resistance involves activation through TLR ligands such
as increased free fatty acids and lipid derivatives from adipocytes as well as the skeletal muscles. Moreover, gut microbiota
alteration in the type 2 diabetes also plays a key role by increasing the plasma LPS levels, which specifically activates
TLR4 and provokes the inflammation mediated insulin resistance. NOD1 and NOD2 are involved in the pathogenesis of
diabetes, possibly through the recognition of the gut microbiota. Gut microbiota modulation by antibiotics plays a crucial
role in increasing insulin sensitivity, possibly through the TLRs and NLRs mediated signaling responses, which suggest
future therapeutic approaches for obesity, insulin resistance and type 2 diabetes. In this review, we focused on the interdependent
role of TLRs and NLRs in metabolic diseases and their cross talk for the pathogenesis of inflammatory diseases.
Antibiotics, gut microbiota, inflammation, NLRs, obesity, TLRs, type 2 diabetes.
Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Chharodi, Ahmedabad-382481, Gujarat, India.