title: Impact of toll-like-receptor-9 (TLR9) deficiency on visceral adipose tissue adipokine expression during chronic DSS-induced colitis in mice.
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.
  
  
  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 TLR9(wt/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.
authors: Department of Internal Medicine III, Giessen University Hospital, Germany.
authors: T
authors: T
authors: Karrasch
authors: Department of Internal Medicine III, Giessen University Hospital, Germany.
authors: A
authors: A
authors: Schmid
authors: Department of Internal Medicine I, Regensburg University Hospital, Germany.
authors: A
authors: A
authors: Kopp
authors: Department of Internal Medicine I, Regensburg University Hospital, Germany.
authors: F
authors: F
authors: Obermeier
authors: Department of Internal Medicine I, Regensburg University Hospital, Germany.
authors: C
authors: C
authors: Hofmann
authors: Department of Internal Medicine III, Giessen University Hospital, Germany.
authors: A
authors: A
authors: Schäffler
mesh_terms: D041721:3T3-L1 Cells; D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*
chemical_list: D054392:Adipokines; D016207:Cytokines; D020738:Leptin; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse