SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice

Tae Il Jeon, Bing Zhu, Jarrod L. Larson, Timothy F. Osborne

Research output: Contribution to journalArticlepeer-review

129 Scopus citations


Bitter taste-sensing G protein-coupled receptors (type 2 taste receptors [T2Rs]) are expressed in taste receptor cells of the tongue, where they play an important role in limiting ingestion of bitter-tasting, potentially toxic compounds. T2Rs are also expressed in gut-derived enteroendocrine cells, where they have also been hypothesized to play a role in limiting toxin absorption. In this study, we have shown that T2R gene expression in both cultured mouse enteroendocrine cells and mouse intestine is regulated by the cholesterol-sensitive SREBP-2. In addition, T2R stimulation of cholecystokinin (CCK) secretion was enhanced directly by SREBP-2 in cultured cells and in mice fed chow supplemented with lovastatin and ezetimibe (L/E) to decrease dietary sterol absorption and increase nuclear activity of SREBP-2. Low-cholesterol diets are naturally composed of high amounts of plant matter that is likely to contain dietary toxins, and CCK is known to improve dietary absorption of fats, slow gastric emptying, and decrease food intake. Thus, these studies suggest that SREBP-2 activation of bitter signaling receptors in the intestine may sensitize the gut to a low-fat diet and to potential accompanying food-borne toxins that make it past the initial aversive response in the mouth.

Original languageEnglish (US)
Pages (from-to)3693-3700
Number of pages8
JournalJournal of Clinical Investigation
Issue number11
StatePublished - Nov 3 2008

ASJC Scopus subject areas

  • General Medicine


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