Activation of TLRs Triggers GLP-1 Secretion in Mice

Abstract

The gastrointestinal tract constitutes a large interface with the inner body and is a crucial barrier against gut microbiota and other pathogens. As soon as this barrier is damaged, pathogen-associated molecular patterns (PAMPs) are recognized by immune system receptors, including toll-like receptors (TLRs). Glucagon-like peptide 1 (GLP-1) is an incretin that was originally involved in glucose metabolism and recently shown to be rapidly and strongly induced by luminal lipopolysaccharides (LPS) through TLR4 activation. In order to investigate whether the activation of TLRs other than TLR4 also increases GLP-1 secretion, we used a polymicrobial infection model through cecal ligation puncture (CLP) in wild-type and TLR4-deficient mice. TLR pathways were assessed by intraperitoneal injection of specific TLR agonists in mice. Our results show that CLP induces GLP-1 secretion both in wild-type and TLR4-deficient mice. CLP and TLR agonists increase gut and systemic inflammation. Thus, the activation of different TLRs increases GLP-1 secretion. This study highlights for the first time that, in addition to an increased inflammatory status, CLP and TLR agonists also strongly induce total GLP-1 secretion. Microbial-induced GLP-1 secretion is therefore not only a TLR4/LPS-cascade.

The Effect of Enteric-Derived Lipopolysaccharides on Obesity

“…Lijuan Wang's [132] experiments also support the idea that LPS affect plasma GLP-1 content via toll-like receptor 4 and that GLP-1 content may reflect intestinal damage to some extent. New research has recently suggested that microbially induced GLP-1 production is not only mediated by LPS and TLR4 but that the activation of other toll-like receptors also leads to increased GLP-1 production [133]. Kahles' [115] study found that LPS dose-and time-dependently increased total serum GLP-1 concentrations in mice, reducing insulin secretion and blood glucose under inflammatory conditions.…”