Substance P, obesity, and gut inflammation

Abstract

Purpose of review: The purpose of this review is to present recent data on the effects of substance P on the development of two common pathological conditions, namely obesity and gut inflammation, and elucidate the role of this neuropeptide as a potential regulator between increased adiposity and exacerbated inflammatory responses during inflammatory bowel disease.

Recent findings: We present data that demonstrate a role for substance P in both obesity and inflammatory bowel disease and investigate potential effects on fat tissue that may influence the progression of intestinal inflammation. More specifically, we discuss new evidence for direct effects of substance P on fat tissue that determine fat depot size and overall weight in mice and analyze some of the potential mechanisms. Furthermore, we present data that describe changes in the intestinal sensory innervation, in particular substance P-positive innervation, during gut inflammation and new direct evidence of the effects of preestablished obesity in the outcome of experimental inflammation of the colon in mice. In the end we propose a link between the role of substance P in the promotion of obesity and the potential consequences on inflammatory bowel disease.

Summary: We propose that substance P may promote fat tissue expansion either centrally or peripherally and thus create a proinflammatory environment (as is the case with obesity) which may in turn affect the progression (exacerbate) of gut inflammation. Further studies are required on the effects of 'creeping fat' in inflammatory bowel disease in order to decipher the role of this type of fat-depot expansion in the development of the disease.

Figure 1

Schematic description on the sequence of events that may link SP with increased mesenteric adipocity and the severity of intestinal inflammation. SP levels increase in the intestinal mucosa during inflammation and signal to the proximal mesenteric fat depots via the destruction of the intestinal wall (alternatively fat cells may be exposed to SP through the sensory neurons innervating these depots). Such an exposure may than lead to increased preadipocytes proliferation and the subsequent fat depot expansion observed in CD (as well as in our experimental models of TNBS colitis). Finally, SP-induced increases in IL-8 expression may lead to increased neutrophil recruitment that in turn have the potential to induce the recruitment of a number of inflammatory cells through cytokine secretion of their own.