Minireview: Peripheral Nesfatin-1 in Regulation of the Gut Activity—15 Years since the Discovery

SIMPLE SUMMARY: Nesfatin-1 is a newly identified molecule derived from the precursor protein NEFA/nucleobindin2. In this minireview we analyzed the research on the nesfatin-1 localization in the gastrointestinal tract of the mammals. We also referred to the effects of the protein on disorders in the gastrointestinal tract. ABSTRACT: Nesfatin-1, discovered in 2006, is an anorexigenic molecule derived from the precursor protein NEFA/nucleobindin2. It is generally postulated that this molecule acts through a specific G protein-coupled receptor, as yet unidentified. Research conducted over the last 15 years has revealed both central and peripheral actions of nesfatin-1. Given its major central role, studies determining its inhibitory effect on food intake seem to be of major scientific interest. However, in recent years a number of experiments have found that peripheral organs, including those of the gastrointestinal tract (GIT), may also be a source (possibly even the predominant source) of nesfatin-1. This mini-review aimed to summarize the current state of knowledge regarding the expression and immunoreactivity of nesfatin-1 and its possible involvement (both physiological and pathological) in the mammalian GIT. Research thus far has shown very promising abilities of nesfatin-1 to restore the balance between pro-oxidants and antioxidants, to interplay with the gut microbiota, and to alter the structure of the intestinal barrier. This necessitates more extensive research on the peripheral actions of this molecule. More in-depth knowledge of such mechanisms (especially those leading to anti-inflammatory and anti-apoptotic effects) is important for a better understanding of the involvement of nefatin-1 in GIT pathophysiological conditions and/or for future therapeutic approaches.