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Exp Clin Endocrinol Diabetes 2015; 123(02): 80-87
DOI: 10.1055/s-0034-1398502
Article
© Georg Thieme Verlag KG Stuttgart · New York

Impact of Toll-like-receptor-9 (TLR9) Deficiency on Visceral Adipose Tissue Adipokine Expression during Chronic DSS-induced Colitis in Mice

T. Karrasch
1   Department of Internal Medicine III, Giessen University Hospital, Germany
,
A. Schmid
1   Department of Internal Medicine III, Giessen University Hospital, Germany
,
A. Kopp
2   Department of Internal Medicine I, Regensburg University Hospital, Germany
,
F. Obermeier
2   Department of Internal Medicine I, Regensburg University Hospital, Germany
,
C. Hofmann
2   Department of Internal Medicine I, Regensburg University Hospital, Germany
,
A. Schäffler
1   Department of Internal Medicine III, Giessen University Hospital, Germany
› Author Affiliations
Further Information

Publication History

received 12 August 2014
first decision 27 November 2014

accepted 17 December 2014

Publication Date:
05 February 2015 (online)

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Abstract

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 TLR9wt/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 TLR9wt/wt mice, while TLR9-/- animals showed a significant reduction of leptin expression even below baseline. While visfatin expression remained unchanged in TLR9wt/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.

Key words

leptin - visfatin - CTRP-3 - IL-6 - visceral adipose tissue - TLR9 - DSS - chronic colitis
 

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