Studies on expression and function of TRPVI in gut implications in metabolic disorders

Abstract

The gut mucus regulation and the role of gastrointestinal TRPV1, both have been largely ignored in metabolic disorder studies. In the present work, we explored these phenomena using in vitro and in vivo models. In vitro findings indicated that the TRPV1 modulators could affect the expression of various mucoregulatory genes. Direct activation of TRPV1 in transfected cell line, confirmed that the gut bacteria and their metabolites were capable of TRPV1 stimulation and resulting Ca2+ signaling. In the in vivo TRPV1 ablation experiment, a direct relation between systemic neuronal TRPV1 ablation, colonic mucus production and gut microbiota was established. The findings indicated that neuronal TRPV1 could be involved in maintaining the gut mucosal homeostasis and microbial population. In metabolic syndrome model, we observed that the prevention of HFD-induced weight gain, improved glucose homeostasis, gut barrier function, and gut microbiota caused by capsaicin, were also reflected by mucin-feeding. This suggested the possible role of mucosal modulation by capsaicin in anti-obesity effects. Improvement in serotonin and CGRP levels by both capsaicin and mucin-feeding further corroborated our hypothesis. Direct, host-independent effect of capsaicin on microbial population and agonistic effect of certain bacteria and their metabolites on TRPV1, suggest that the capsaicin-TRPV1-mucus-microbiota interaction works in a cyclic cascade. Further studies in this direction will lead to a better approach towards employing interventions of dietary origins against diet-induced metabolic complications as well as disorders related to gastrointestinal inflammation. newline