Karrasch, T. and Schmid, A. and Kopp, A. and Obermeier, F. and Hofmann, C. and Schaeffler, A. (2015) Impact of Toll-like-receptor-9 (TLR9) Deficiency on Visceral Adipose Tissue Adipokine Expression during Chronic DSS-induced Colitis in Mice. EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 123 (2). pp. 80-87. ISSN 0947-7349, 1439-3646
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; CREEPING FAT; C1Q/TNF-RELATED PROTEIN-3; CELL-LINE; ADIPOCYTE DIFFERENTIATION; INTESTINAL INFLAMMATION; PERIPANCREATIC NECROSIS; ULCERATIVE-COLITIS; CIRCULATING LEVELS; leptin; visfatin; CTRP-3; IL-6; visceral adipose tissue; TLR9; DSS; chronic colitis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jul 2019 12:56 |
| Last Modified: | 24 Jul 2019 12:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5993 |
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