Sugar is a fundamental source of energy for all animals and, correspondingly, most species have evolved dedicated brain circuits to seek, recognize and motivate consumption of sugar. In humans, recruitment of these circuits for reward and pleasure — rather than nutritional needs — is believed to be an important contributor to the overconsumption of sugar in our society and the concomitant increase in obesity rates. Comparing the 21st century to the 1800s, the average American today consumes more than 10 times as much sugar…!!
Sweet compounds are detected by specific taste receptor cells on the tongue and palate epithelium. Activation of sweet taste receptor cells sends hard-wired signals to the brain to elicit recognition of sweet-tasting compounds. What are the circuits that are used to link activation of sweet taste receptors on the tongue to sweet-evoked attraction? Surprisingly, even in the absence of a functional sweet-taste pathway, animals can still acquire a preference for sugar. Furthermore, although artificial sweeteners activate the same sweet taste receptor as sugars (and they may do so with vastly higher binding affinities), they fail to substitute for sugar in generating a behavioral preference. Together, these results suggest the existence of a sugar-specific — rather than sweet-taste-specific — pathway that operates independently of the sense of taste to create preference for sugar and motivate its consumption. Authors [see attached article] therefore examined the neural basis for sugar preference.
When non-thirsty wild-type mice are given a choice between water and sugar — they drink almost exclusively from the sugar solution. If they are allowed to choose between an artificial sweetener (e.g. acesulfame K) and sugar, naïve mice initially drink from both bottles at a similar rate. However, within 24 h of exposure to both choices, their preference changes such that by 48 h — they drink almost exclusively from the bottle containing sugar. This behavioral switch also happens in knockout (KO) mice lacking the sweet taste receptors TRPM5 and T1R2/3 [similar observations have been made in several studies, primarily using flavor-conditioning assays]. Thus, although taste-knockout mice cannot taste sugar or sweetener, they learn to recognize and choose sugar, most probably as a result of strong “positive” effects after eating (post-ingestive effects).
Using functional imaging, authors monitored activity of the gut–brain axis and identified vagal neurons (located between the aorta and esophagus; this is the end of the recurrent nerve) activated by intestinal delivery of glucose. Engineering mice in which synaptic activity in this gut-to-brain circuit was genetically silenced — prevented the development of behavioral preference for sugar. Next, authors showed that appropriating this circuit by chemogenetic activation creates preferences to otherwise less-preferred stimuli. These findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. These data further explain the neural basis for differences in the behavioral effects of sweeteners versus sugar. These findings have uncovered an essential circuit underlying the enjoyable effects of sugar satisfaction. 😊
DwN
Nature 23 Apr 2020; 580: 511-516