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

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 5

CCK secretion in STC-1 cells is regulated by T2R138 agonist through SREBP-2.

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CCK secretion in STC-1 cells is regulated by T2R138 agonist through SREB...
(A) STC-1 cells in 12-well microplates were transfected with an siRNA targeting mT2R138 or control siRNA (10 nM). Forty-eight hours after transfection, medium was removed and cultures were rinsed with PBS, and cells were cultured in the absence or presence of sterols (12 μg/ml cholesterol and 1 μg/ml 25-hydroxycholesterol); where indicated, atorvastatin (1 μM) was included. After 24-hour incubation, cells were treated with PTC (10 mM final concentration) for 45 minutes. The media and cells were collected and analyzed for CCK by EIA or RNA levels by RT-qPCR. (B) STC-1 cells in 6-well microplates were infected with Ad-DN-SREBP or Ad-GFP (10 MOI) for 24 hours and analyzed as in A. Data are mean ± SEM; n = 5 for 5 separate experiments. §P < 0.05, †P < 0.01, #P < 0.001, *P = NS versus control. NCi, negative control siRNA.