Abstract
BackgroundInflammation is a major component of obesity and diabetes, and toll-like receptors (TLRs) play critical roles in the regulation of inflammation and response to pathogen associated molecular patterns (PAMPs) and fatty acids in. Although immune cells such as macrophages are primarily responsible for recognition and clearance of pathogens, 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.MethodsWe investigated the response to peptidoglycan from Staphylococcus aureus in differentiated 3T3-L1 adipocytes. Real-time PCR analysis was used to quantify the expression of interleukin 6 (IL6), adiponectin receptors (adipoR1 and adipoR2), toll-like receptor 2 (TLR2) and 4 (TLR2 4). Media level of IL6 was determined with ELISA.ResultsAdipocyte 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 lipopolysaccharide (LPS) robustly induce 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).ConclusionObesity 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.
Highlights
Inflammation is a major component of obesity and diabetes, and toll-like receptors (TLRs) play critical roles in the regulation of inflammation and response to pathogen associated molecular patterns (PAMPs) and fatty acids in
toll-like receptor 2 (TLR2) expression is significantly increased in adipose tissue of type 2 diabetic and obese patients and its expression is upregulated by resistin, an hormone that induces insulin resistance, suggesting TLR2 may be intricately involved in the regulation of inflammationinduced insulin resistance than hitherto recognized [8,9]
Because fatty acids are directly implicated in the induction of inflammation in adipocytes via TLR4 activation [7], and circulating fatty acid concentrations are elevated in obesity, we further explored the possibility that fatty acids exert a direct role in the regulation of TLR2 and TLR4 expression, indirectly influencing the inflammatory response in adipocytes
Summary
Inflammation is a major component of obesity and diabetes, and toll-like receptors (TLRs) play critical roles in the regulation of inflammation and response to pathogen associated molecular patterns (PAMPs) and fatty acids in. Toll-like receptor 2 is the most promiscuous of all the TLRs and is able to recognize multiple ligands such as fatty acids, fungal zymosan and gram positive bacteria components (peptidoglycan and teichoic acid), lipoarabinomanan, bacterial lipopeptides, some LPS variants from gram-negative bacteria, yeast, spirochetes and fungi [11,12]. This receptor is able to form heterodimers with other TLRs [13]. The identities of its ligands in vivo have not been clarified, we explored the possibility that mature adipocytes respond directly in vitro to a gram positive bacteria component
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