Zusammenfassung
Background: Studies postulate an involvement of adipokines in inflammatory gastrointestinal diseases. Leptin-deficient ob/ ob mice as well as TLR9-deficient mice have a more moderate course of chronic DSS-induced colitis ( DSS-CC) and adipocytes do express functional TLR9 molecules. Material and Methods: Adipokine mRNA expression in visceral adipose tissue of mice before and after the induction ...
Zusammenfassung
Background: Studies postulate an involvement of adipokines in inflammatory gastrointestinal diseases. Leptin-deficient ob/ ob mice as well as TLR9-deficient mice have a more moderate course of chronic DSS-induced colitis ( DSS-CC) and adipocytes do express functional TLR9 molecules. Material and Methods: Adipokine mRNA expression in visceral adipose tissue of mice before and after the induction of DSS-CC was investigated. Experiments were performed in both TLR9(wt/wt) and TLR9(-/)-mice. In vitro, the effect of TLR9 blocking peptide on leptin and visfatin protein secretion was studied in 3T3-L1 adipocytes. Results: Induction of DSS-CC led to an upregulation of leptin mRNA expression in TLR9(wt/wt) mice, while TLR9-/-animals showed a significant reduction of leptin expression even below baseline. While visfatin expression remained unchanged in TLR9(wt/wt) animals, TLR9(-/)-mice exhibited a significant induction during DSS-CC. CTRP-3 expression was reduced after colitis induction only in TLR9-/-animals. Of note, IL-6 expression levels remained unchanged, while CXCL1/ KC and cyclophilin A expression was reduced in DSS-CC. Inhibition of TLR9 signaling by using TLR9 blocking peptide led to reduced leptin protein secretion into cell culture supernatants in 3T3-L1 adipocytes, while visfatin protein secretion was enhanced. Conclusions: DSS-CC leads to differential adipokine expression profiles in the visceral fat pad in TLR9wt/ wt vs. TLR9-/-mice. In vitro, inhibition of TLR9 signaling induces visfatin secretion while inhibiting leptin secretion in adipocytes. Thus, visceral adipokines are regulated by intact TLR9 signaling pathway and a specific interplay between the leptin-and the TLR9-pathways might be of pathophysiological importance in chronic intestinal inflammation.
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