title: Citrus flavonoid naringenin inhibits TLR2 expression in adipocytes.
abstract: Toll-like receptors (TLRs) were recently shown to be involved in obesity-induced inflammation in adipose tissue, which contributes to the development of insulin resistance and type 2 diabetes. Thus, the appropriate regulation of TLR expression or activation is an important strategy for improving obesity-related diseases. In this report, we show that naringenin, a citrus flavonoid, inhibits TLR2 expression during adipocyte differentiation. This effect is mediated in part through peroxisome proliferator-activated receptor γ activation. In addition, naringenin suppresses TLR2 expression induced by the co-culture of differentiated adipocytes and macrophages and also inhibits tumor necrosis factor-α (TNF-α)-induced TLR2 expression by inhibiting the activation of nuclear factor-κB and c-Jun NH2-terminal kinase pathways in differentiated adipocytes. Furthermore, naringenin decreases TLR2 expression in adipose tissue of high-fat diet-fed mice. These results are correlated with the improvement of hyperglycemia and the suppression of inflammatory mediators, including TNF-α and monocyte chemotactic protein-1. Taken together, these data suggest that naringenin exhibits anti-inflammatory properties, presumably by inhibiting TLR2 expression in adipocytes. Our findings suggest a molecular mechanism by which naringenin exerts beneficial effects against obesity-related diseases.
authors: Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka City, Miyazaki 882-8508, Japan. h-yoshida@phoenix.ac.jp
authors: Hiroki
authors: H
authors: Yoshida
authors: Wataru
authors: W
authors: Watanabe
authors: Hiroyuki
authors: H
authors: Oomagari
authors: Eisuke
authors: E
authors: Tsuruta
authors: Mikiko
authors: M
authors: Shida
authors: Masahiko
authors: M
authors: Kurokawa
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002957:Citrus / Q000737:chemistry*; D018920:Coculture Techniques; D044950:Flavanones / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D044950:Flavanones; D016328:NF-kappa B; D047495:PPAR gamma; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D048670:MAP Kinase Kinase 4; C005273:naringenin