Inflammation is a major component of obesity and diabetes. Toll-like receptors (TLRs) play critical roles in the regulation of inflammation in adipocytes in response to pathogen associated molecular patterns (PAMPs), fatty acids, and extracellular matrix proteins. Although immune cells are primarily responsible for recognition and clearance of pathogens, current evidence indicates that adipocytes are also closely involved in the regulation of innate immunity and inflammation. Whereas it has been demonstrated that adipocytes respond to TLR4 stimulation with lipopolysacccharide, very little is known about their response to the TLR2 agonist, peptidoglycan. We investigated herein adipocyte response to peptidoglycan from Staphylococcus aureus, a gram positive bacteria. Adipocyte stimulation peptidoglycan induces IL6 expression (P < 0.01). Both siRNA mediated suppression of TLR2 and immunoneutralization of TLR2 with a TLR2 specific antibody inhibited response to peptidoglycan (P< 0.05). We also examined the regulation of TLR2 and TLR4 mRNA in peptidoglycan treated cells. Both peptidoglycan and LPS robustly induced TLR2 mRNA expression, whereas TLR4 mRNA is weakly induced by LPS only (P < 0.05). Additionally, peptidoglycan downregulates the mRNA expression of adiponectin receptors, adipoR1 and adipoR2 (P < 0.05). Because obesity and type 2 diabetes are associated with increased expression of TLR2, this receptor could play a significant but previously unrecognized role in the establishment of chronic inflammation in adipose tissue in obesity.KEYWORDS:Adipocytes; peptidoglycan; inflammation; gram positive bacteria; TLRs, adipoR1, adipoR2