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SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice
Tae-Il Jeon, … , Jarrod L. Larson, Timothy F. Osborne
Tae-Il Jeon, … , Jarrod L. Larson, Timothy F. Osborne
Published October 9, 2008
Citation Information: J Clin Invest. 2008;118(11):3693-3700. https://doi.org/10.1172/JCI36461.
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Research Article Genetics

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

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Abstract

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.

Authors

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

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Figure 2

SREBP-2 induces T2R138 expression in STC-1 cells.

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SREBP-2 induces T2R138 expression in STC-1 cells.
STC-1 cells were plate...
STC-1 cells were plated and incubated for 24 hours in medium containing or lacking additional sterols (12 μg/ml cholesterol and 1 μg/ml 25-hydroxycholesterol) or lacking sterols but with atorvastatin (10 μM) as described in Methods. (A) mRNA levels for SREBP-2 and T2R138 were analyzed by RT-qPCR. (B) Whole cell lysates were analyzed for SREBP-2 or T2R138 protein levels by immunoblotting. Data are representative of 3 separate experiments. (C) STC-1 cells were infected with Ad-hSREBP-2 or Ad-GFP for 24 hours, and mRNA levels of human (virus-encoded) or endogenous mouse SREBP-2, HMG Co-A reductase (HMGCR), and T2R138 were analyzed by RT-qPCR. Data are mean ± SEM; n = 3 for 3 separate experiments. S+, sterols+; S–, sterols–; AS, atorvastatin.

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