Exp Clin Endocrinol Diabetes 2015; 123 - P05_06
DOI: 10.1055/s-0035-1547681

Visceral adipokine expression profiles are significantly altered in TLR9-/- mice during chronic DSS-induced colitis

T Karrasch 1, J Schlegel 2, A Schmid 1, F Obermeier 3, C Hofmann 3, A Schäffler 4
  • 1Klinik und Poliklinik für Innere Medizin III; Universitätsklinikum Gießen und Marburg, Standort Gießen
  • 2Endokrinologisches Forschungslabor; Innere Medizin III
  • 3Klinik für Innere Medizin I; Universitätsklinikum Regensburg
  • 4Universitätsklinikum Gießen; Medizinische Klinik und Poliklinik III

Adipokines profoundly impact on the homeostasis of the whole organism. During gastrointestinal inflammation, visceral adipose tissue is of particular importance. Recently, it has been demonstrated that adipocytes express functional TLR9 receptors. Leptin-deficient ob/ob mice as well as TLR9-/- mice are characterized by an attenuated course of an experimental dextran-sodium-sulfat (DSS) induced chronic colitis (DSS-CC).

We investigated adipokine mRNA expression in visceral adiose tissue of mice suffering from DSS-CC versus healthy controls. To characterize the influence of functional TLR9 signaling, experiments were performed in TLR9wt/wt versus TLR9-/- mice. Additionally, the impact of inhibiting TRL9 signaling on adipokine protein secretion was investigated in 3T3-L1 adipocytes in vitro.

TLR9wt/wt mice exhibited a profound increase in visceral adipose tissue leptin mRNA expression after induction of a DSS-CC, while leptin expression in colitic TLR9-/- mice was significantly reduced. TLR9-/- mice also showed reduced anti-inflammatory CTRP-3 and increased visfatin mRNA expression during DSS-CC, which were not found in TRL9wt/wt mice. CXCL1/KC and Cyclophilin A were decreased during colitis independent of the genotype. In vitro inhibition of TRL9 signaling by TLR9 blocking peptide led to a significantly reduced leptin and increased visfatin protein secretion in cell culture supernatants of 3T3-L1 adipocytes.

The adipokine expression profile of visceral adipose tissue during DSS-CC is significantly altered in TLR9-/- mice as compared to TLR9wt/wt mice. In vitro the inhibition of TLR9 signal transduction leads to an induction of visfatin secretion while simultaneously inhibiting leptin secretion in adipocytes. We postulate a molecular link (metabolic gate) and adaptation of homeostatic metabolic processes to local and systemic inflammation. In this context, the interaction of leptin and TLR9 signaling could play a central role during gastrointestinal inflammation.