Diet-Induced Regulation of Bitter Taste Receptor Subtypes in the Mouse Gastrointestinal Tract

Gaia Vegezzi,Laura Anselmi,Helen Raybould,Jennifer Huynh,Elisabetta Barocelli,Catia Sternini,Enrique Rozengurt,Gunnar Loh

doi:10.1371/journal.pone.0107732

Abstract

Bitter taste receptors and signaling molecules, which detect bitter taste in the mouth, are expressed in the gut mucosa. In this study, we tested whether two distinct bitter taste receptors, the bitter taste receptor 138 (T2R138), selectively activated by isothiocyanates, and the broadly tuned bitter taste receptor 108 (T2R108) are regulated by luminal content. Quantitative RT-PCR analysis showed that T2R138 transcript is more abundant in the colon than the small intestine and lowest in the stomach, whereas T2R108 mRNA is more abundant in the stomach compared to the intestine. Both transcripts in the stomach were markedly reduced by fasting and restored to normal levels after 4 hours re-feeding. A cholesterol-lowering diet, mimicking a diet naturally low in cholesterol and rich in bitter substances, increased T2R138 transcript, but not T2R108, in duodenum and jejunum, and not in ileum and colon. Long-term ingestion of high-fat diet increased T2R138 RNA, but not T2R108, in the colon. Similarly, α-gustducin, a bitter taste receptor signaling molecule, was reduced by fasting in the stomach and increased by lowering cholesterol in the small intestine and by high-fat diet in the colon. These data show that both short and long term changes in the luminal contents alter expression of bitter taste receptors and associated signaling molecules in the mucosa, supporting the proposed role of bitter taste receptors in luminal chemosensing in the gastrointestinal tract. Bitter taste receptors might serve as regulatory and defensive mechanism to control gut function and food intake and protect the body from the luminal environment.

Highlights

The sense of taste is important to evaluate the quality of nutrients and distinguish between safe and dangerous food prior to ingestion [1,2]
T2R108 mRNA expression was more abundant in the stomach, followed by colon and small intestine. a-gustducin transcript was distributed throughout the GI tract with the highest levels in the stomach and colon
Specificity of immunoreaction was demonstrated by the strong labeling of taste bud cells in the tongue (Fig 2A) and immunoblocking experiments showing abolition of T2R138 (Fig 2C) or a-gustducin immunostaining when antibodies were pre-incubated with an excess of the appropriate peptide

Summary

Introduction

The sense of taste is important to evaluate the quality of nutrients and distinguish between safe and dangerous food prior to ingestion [1,2]. Expression of sweet/umami (T1R) and bitter (T2R) taste receptors and their signaling molecules has been reported in several extraoral sites including the digestive [11,12,13,14,15,16], respiratory [17,18,19,20,21,22] and reproductive systems [23,24], and the brain [25] strongly supporting the concept that there is more than a ‘‘taste’’ function for taste receptors and that they exert non-gustatory functions outside the mouth, which might vary according to the site of expression [4,26]

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Results

Conclusion