Endocannabinoids selectively enhance sweet taste

Abstract

Endocannabinoids such as anandamide [N-arachidonoylethanolamine (AEA)] and 2-arachidonoyl glycerol (2-AG) are known orexigenic mediators that act via CB 1 receptors in hypothalamus and limbic forebrain to induce appetite and stimulate food intake. Circulating endocannabinoid levels inversely correlate with plasma levels of leptin, an anorexigenic mediator that reduces food intake by acting on hypothalamic receptors. Recently, taste has been found to be a peripheral target of leptin. Leptin selectively suppresses sweet taste responses in wild-type mice but not in leptin receptor-deficient db/db mice. Here, we show that endocannabinoids oppose the action of leptin to act as enhancers of sweet taste. We found that administration of AEA or 2-AG increases gustatory nerve responses to sweeteners in a concentration-dependent manner without affecting responses to salty, sour, bitter, and umami compounds. The cannabinoids increase behavioral responses to sweet-bitter mixtures and electrophysiological responses of taste receptor cells to sweet compounds. Mice genetically lacking CB 1 receptors show no enhancement by endocannnabinoids of sweet taste responses at cellular, nerve, or behavioral levels. In addition, the effects of endocannabinoids on sweet taste responses of taste cells are diminished by AM251, a CB 1 receptor antagonist, but not by AM630, a CB 2 receptor antagonist. Immunohistochemistry shows that CB 1 receptors are expressed in type II taste cells that also express the T1r3 sweet taste receptor component. Taken together, these observations suggest that the taste organ is a peripheral target of endocannabinoids. Reciprocal regulation of peripheral sweet taste reception by endocannabinoids and leptin may contribute to their opposing actions on food intake and play an important role in regulating energy homeostasis.energy homeostasis | gustation | reciprocal regulation E ndocannabinoids such as anandamide [N-arachidonoylethanolamine (AEA)] and 2-arachidonoyl glycerol (2-AG) are known orexigenic mediators that act via CB 1 receptors in hypothalamus and limbic forebrain to induce appetite (1, 2) and stimulate food intake (3). Systemic administration of exogenous cannabinoids or endocannabinoids in rodents causes hyperphagia (4) and increases the preference for palatable substances such as sucrose solution or food pellets (5, 6). These effects are mediated by the CB 1 receptor: pretreatment with the CB 1 antagonist SR141716 inhibited hyperphagia and reduced consumption of both bland and palatable foods (4-6). The natural "liking" reactions of rats to sweet compounds were amplified by endogenous cannabinoid signals in nucleus accumbens (7). Thus, endocannabinoids may be related to hedonic aspects of sweet taste.There is growing evidence that taste function can be modulated by hormones or other factors that act on receptors present in the peripheral gustatory system. Leptin, an anorexigenic mediator that reduces food intake by acting on hypothalamic receptors (8), selectively suppresses sweet taste responses and th...

Taste perception, associated hormonal modulation, and nutrient intake

“…Hormones that bind to receptors on taste cells alter the palatability of food and, therefore, intake. Current knowledge of the hormonal modulation of taste function is summarized in Table 1 [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] and described in greater detail below.…”

The Endocannabinoid 2-Arachidonoyl-Glycerol Controls Odor Sensitivity in Larvae of Xenopus laevis

“…Blockage of cannabinoid CB 1 receptors diminishes and delays responses to food odorants (Czesnik et al, 2007). Furthermore, CB 1 receptors in type II taste cells have been shown recently to participate in the enhancement of sweet taste (Yoshida et al, 2010).…”

Modulation of Taste Responsiveness by Angiotensin II

“…It was recently revealed that endocannabinoids enhance sweet taste sensitivity via CB1 in peripheral T1r3 expressing sweet taste cells (Yoshida et al, 2010). Moreover, AT1 and CB1 form receptor heteromers, resulting in the potentiation of AT1 signaling in hepatic stellate cells from ethanol-administered rats (Rozenfeld et al, 2011).…”