Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes.
Chronic inflammation is closely associated with metabolic disorders such as obesity and type 2 diabetes, however, the underlying mechanism is unclear. Toll-like receptors (TLRs) play a key role in innate immune response as well as inflammatory signals. Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes.
Song
Min Jeong
MJ
Department of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Republic of Korea.
Kim
Kang Ho
KH
Yoon
Jeong Min
JM
Kim
Jae Bum
JB
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D013229:Stearic Acids / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013229:Stearic Acids; D051197:Toll-Like Receptor 4; C031183:stearic acid; D005947:Glucose