A low-cholesterol diet leaves a bitter taste in the gut

One role for the proteins on the tongue that sense bitter tasting substances, type 2 taste receptors (T2Rs), is to limit ingestion of these substances, as a large number of natural bitter compounds are known to be toxic. T2Rs are also found in the gut, and it has been suggested that there they have a similar role to their function in the mouth (i.e., they might limit intestinal toxin absorption). Data to support this idea has now been generated in mice by Timothy Osborne and colleagues, at the University of California, Irvine.

By supplementing the food that mice eat with the drugs lovastatin and ezetimibe (L/E), it is possible to reduce the amount of cholesterol that they take up, and they are therefore considered to be consuming a low-cholesterol diet. Such a diet increases the activity of the protein SREBP-2 in the gut. In this study, SREBP-2 was shown to directly induce the expression of T2Rs in cultured mouse intestinal cells as well as in the intestine of mice consuming food supplemented with L/E. In addition, SREBP-2 was shown to directly enhance T2R-induced secretion of the intestinal peptide cholecystokinin in both the cultured mouse intestinal cells and mice consuming food supplemented with L/E. As low-cholesterol diets are naturally composed of high amounts of plant matter that is likely to contain dietary toxins, and one function of cholecystokinin is to decrease food intake, the authors suggest that SREBP-2–induced expression of T2Rs might provide a mechanism both to inform the gut that food-borne toxins could be present and to initiate a response that limits their absorption.

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

AUTHOR CONTACT:
Timothy F. Osborne
University of California at Irvine, Irvine, California, USA.
Phone: (949) 824-2979; Fax: (949) 824-8551; E-mail: tfosborn@uci.edu.

MEDIA CONTACT:
Jennifer Fitzenberger
Assistant Director of Media Relations
University of California at Irvine, Irvine, California, USA.
Phone: (949) 824-3969; E-mail: jfitzen@uci.edu.

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