Editors' ChoiceObesity

Supersweet: This Is Your Taste Buds on Dope

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Science Translational Medicine  20 Jan 2010:
Vol. 2, Issue 15, pp. 15ec9
DOI: 10.1126/scitranslmed.3000823

Although not as well known as its exogenous relative cannabis, endocannabinoids are endogenous lipid signaling molecules that bind to cannabinoid receptors (CB1 and CB2)–the same molecules targeted by tetrahydrocannabinol, the active ingredient of marijuana. The endocannabinoid signaling system participates in almost every major biological function of the human body, and most well-recognized is its role in metabolism. Obese subjects are known to display hyperactivated endocannabinoid signaling in the brain and peripheral tissues relative to nonobese subjects, and CB1 antagonists are effective weight-loss drugs that also improve glucose and lipid homeostasis. As such, these agents are potential weapons in the battle against the rising tide of obesity and type 2 diabetes. However, these drugs can also cause depression and suicidal tendencies, presumably through brain effects, and thus are not approved by the U.S. Food and Drug Administration. In order to develop more targeted anti-obesity drugs without these side effects, researchers need to tweeze apart the myriad effects of endocannabinoid signaling in regulating food intake and energy homeostasis. In a recent paper in PNAS, Yoshida et al., deciphered an important mechanism behind the munchies associated with cannabinoid use.

The hedonic aspects of food intake play a critical role in the obesity epidemic. Systemic administration of exogenous cannabinoids or endocannabinoids in rodents causes excessive hunger and strengthens the preference for palatable substances such as sucrose. To work out the mechanism behind this behavior, the authors investigated whether cannabinoids affect sweet-taste perception at the level of the taste buds. They demonstrate that sweet-taste responses are selectively enhanced by the administration of endocannabinoids, whereas the preferences for the remaining four taste qualities–salty, sour, bitter, or umami ("savory/meat")–are not affected by agents that modulate endocannabinoid signaling. These sweet-enhancing effects of endocannabinoids were completely absent in mice in which the gene CB1 had been knocked out. Furthermore, the authors show that CB1 is coexpressed in taste cells along with the sweet receptor component T1r3 and that the endocannabinoid signaling system regulates taste-cell responses and the activity of sensory neurons that carry impulses from the taste buds to the brain. These findings support the concept that the endocannabinoid signaling system regulates sweet-taste perception through peripheral effects.

The new results raise the following questions: If one deletes CB1 from taste bud cells that express T1r3, would this be sufficient to ameliorate high-fat feeding–induced obesity? Sweet-taste receptors also are found in the intestine, where they facilitate nutrient absorption, insulin secretion, and energy metabolism through the release of a member of the incretin family of hormones, glucagon-like peptide 1, which boosts insulin secretion. Thus, one also must probe whether the endocannabinoid signaling system in the intestine regulates incretin secretion. The current study provides important leads on these and other questions and suggests that peripherally restricted CB1 antagonists might help us control our sweet tooth.

R. Yoshida et al., Endocannabinoids selectively enhance sweet taste. Proc. Natl. Acad. Sci. USA 107, 935–939 (2010). [Full Text]

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