Taster’s Choice: The Endocrinology of the Tongue

As obesity and diabetes rates reach epidemic proportions, a presentation at ENDO 2018 explains why we eat what we eat. We talked with Josephine M. Egan, MD, for a taste of what you can expect from her talk entitled, “Endocrinology of the Tongue.”

On Monday afternoon, March 19, Josephine M. Egan, MD, a senior investigator at the National Institutes of Health and an expert on diabetes and metabolism, will give a talk titled, “Endocrinology of the Tongue,” as part of a larger session that deals with why people eat what they eat, and the larger implications associated with diet as the obesity rates continue to rise.

“Endocrinology of the Tongue” will focus on how mammals evolved to eat, by not only seeking out calories but wanting those calories to act as a reward that includes “feeling good.” For the most part, that means that mammals typically seek out sweet tastes and avoid bitter or sour tastes. However, Egan says that before the 1960s, when humans perceived a sweet taste, it meant they were enjoying the benefits of the calories and energy that came along with it. Now, with the introduction of artificial sweeteners, that’s no longer the case, since these sweeteners, in effect, uncoupled taste from nutrition.

According to Egan, “gut” hormones are produced in taste cells, and these hormones help the mammal perceive the intensity of the chemical stimulus. In this case, the taste and subsequent reward of whatever the meal they’re eating. Egan’s laboratory is primarily interested in beta cell function, and she and her team have been studying incretin physiology and incretin effects in islets for a long time: incretins are hormones secreted from the gut in response to foods that are enhancers of glucose-mediated insulin secretion. “We noticed that mice lacking the receptor for GLP-1 (GLP-1RKO mice) were actually gaining less weight as they aged,” she says. “Yet, the expectation would be that they should maybe gain a little more weight than their wild type littermates with age.”

This revelation made Egan and her team curious, and when they looked further into it, they noticed that the GLP-1R mice did not eat as much of their chow because they did not perceive sweet taste to the same extent as wild type mice. “In other words, their chow was not palatable to them,” she says. “That led us to investigate if GLP-1 was produced in taste cells and if it might be involved in regulating taste cell function.”

Taste Pathways

There are five prototypic tastes: sweet, bitter, sour, salty, and umami (the taste of broths, amino acids such as glutamate). Egan says that these tastes are perceived in the insula within the cortex of the brain and that taste is coded bilaterally in the insulae. Cranial nerves relay the information from the taste cells to the insula, going through ‘relay’ stations on the way.

Egan describes the pathway like this: There are four taste cell types in taste buds — types 1, 2, and 3, with the last type sometimes called a basal cell, a precursor cell, or type 4 cell. The first three cell types are replenished, whenever they undergo apoptosis, from the type 4 cells. What we consider ‘classical’ gut hormones are present in populations of type 1, 2, and 3, depending on the hormone. The hormones are regulating the signaling downstream of when a ‘tastant’ engages its receptor.

“There is still much research to be done on just about every hormone that has ever been isolated and described. I would want endocrinologists to take away a basic knowledge of how we ‘taste’ our food. Textbooks of endocrinology do not cover this, and physiology books are out of date on taste and taste mechanisms.”

But here’s where it gets tricky. With the introduction of these non-caloric artificial sweeteners, these receptors are having different reactions. Egan points to the fact that heavy consumers of non-nutritive sweetened drinks are at higher risk of being obese, which means that artificial sweeteners and sugar evoke a different quality and level of brain responses compared with calorie dense sugars.

“We are beginning to unravel how this is occurring. Based on very elegant studies in mice, we know that there are separate dopaminargic brain circuits for the hedonic and nutritive responses to sugar,” she says. “The separation of the post-ingestive effects of sugar means the energy value of sugar is the prime motivation for its ingestion. Consumption of sugar leads to dopamine release in the nucleus accumbens, an area associated with motivation, novelty, and reward.”

Gut Check

Non-caloric artificial sweeteners are ubiquitous in the modern diet, and yet obesity rates continue to climb. Egan says that’s leading researchers to understand that sweetness, per se, is not the driving force, the ultimate goal, in food intake. “Undoubtedly sweetness enjoys a much more privileged position as a taste in contrast to the variable responses to sour and bitter tastes,” she says. “No culture or species rejects sweetness as unpleasant. Anthropologically this could be ascribed to the sweet taste indicating edibility. This notion is supported by the fact that we evolved from arboreal-dwelling primates that consumed huge quantities of fruit for which the ability to sense sweetness is imperative to avoid being poisoned by fruit that is stale or food that is bitter or sour. However, because of those studies in mice, we know that absorption of calorie-rich foods directly influences the brain’s reward circuitry independent of taste perception.”

“The separation of the post-ingestive effects of sugar means the energy value of sugar is the prime motivation for its ingestion. Consumption of sugar leads to dopamine release in the nucleus accumbens, an area associated with motivation, novelty, and reward.”

This knowledge is another potential front in the battle against obesity and diabetes. Egan says that this work has opened up the field to an understanding that gut hormones like GLP-1 serve a previously undescribed function to modulate responses to taste which in turn can change food consumption. And taste receptors on enteroendorcine cells in the gut have come under investigation as potential targets to stimulate endogenous production of GLP-1 as treatments for pre-diabetes and diabetes.

Egan says that as time goes on, endocrinologists are finding that hormones serve many functions, not just the first functions that were ascribed to them. GLP-1 was first isolated from endocrine cells in the gut and endocrinologists now know it is synthesized in taste cells and subpopulations of neurons. “There is still much research to be done on just about every hormone that has ever been isolated and described,” she says. “I would want endocrinologists to take away a basic knowledge of how we ‘taste’ our food. Textbooks of endocrinology do not cover this, and physiology books are out of date on taste and taste mechanisms.”

Bagley is the senior editor of Endocrine News. He wrote about the Meet the Professor Session at ENDO 2018 by Lisa Tannock, MD, on statin intolerance, in the February issue. 

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