MCH Neurones give the brain sweet tooth

06 January 2014

Interview with

Jeffrey Friedman, Rockefeller University, New York

Why does the brain prefer sucrose over sweeteners? The MCH+ brain cellsneuronal cell population that gives sugar its appealing qualities has been discovered... 

Jeffrey - Sugar is a very attractive nutrient for two reasons. One, it tastes sweet, but is also attractive because it has nutrient value and it's actually the nutrient value of sugar, meaning its ability to provide calories, that explains a lot about why sugar or sucrose in particular is preferred to artificial sweeteners which don't have any nutrient value.

Chris - But I'll put it to you that lots of people do drink diet drinks or they do add sweeteners. So, they obviously do think that the flavour is quite nice. So, when you do subvert your sense systems into experiencing a sweet taste with no calories in it versus glucose, which is obviously more calorie-rich, how does the brain respond to that?

Jeffrey - If animals are given the choice between a natural sugar like sucrose or an artificial sweetener, they invariably prefer the natural sugar. The same is probably true in humans, because all the statistics would seem to indicate sweetened sodas outsell diet sodas by a great margin. Now, it's true that many people use artificial sweeteners and in the short-term of course, they'll find that satisfying but what that doesn't tell you is whether they might go back and have sucrose in some other form later on in the form of a candy bar or a candy. It really seems as if a lot of the intake of sugar and nutrient in general, is unconscious and is driven by signals of the nutrient value that is present in our food.

Chris - Now what actually detects that nutrient value then? So, when I put something sweet into my mouth, is it just the sweet taste and there's therefore a neurological inference of the calorie value of what I'm eating or is there integration of multiple analyses of the food, the calories coming in, plus the sweet taste, or is the brain just looking at blood glucose and going, "Ah! I ate that Mars bar, therefore the sugar's gone up, therefore it must be good for me!"

Jeffrey - The answer appears to be both. So, certainly a sweet taste such as either a sucrose or an artificial sugar, is attractive. But it's attractive because it predicts that that nutrient or that compound you just ate will have calories or nutrient value in it. But if that taste is empty of calories, it won't be reinforced. What reinforced the desire to eat sweet things is ultimately the presence on top of it, of calories which are to some extent thought to be sensed by increase in the level of glucose in the blood. Unknown until recently, however, was where and how that glucose increase in the blood is sensed.

Chris - So, how did you probe that?

Jeffrey - A very talented colleague of mine, Ana Domingos, hypothesised that a particular nerve cell population in the brain referred to as MCH - Melanin Concentrating Hormone - might have something to do with the sensing of sucrose and why it is preferred to sucralose. The reason that Ana hypothesised these neurons might play a role in sugar sensing is because, firstly, the neurons can be shown to fire more rapidly when exposed to sugar, and secondly, because if you kill these neurons, animals lose weight and weigh less. And those two published findings that are to hypothesise that perhaps these neurons played some role in the sensing of sucrose and establishing a preference versus an artificial sweetener.

Chris - Do you think that sensing goes on when the glucose, which just come from the sucrose, goes into the brain or do you think that there are sensors for sweetness in the tongue, perhaps even in the intestine, and they're telling those MCH cells in the brain, "Hey! I'm being stimulated by something sweet"?

Jeffrey - So, the experiment Ana did was, in the first case, kill all the MCH neurons and if you did that, animals could no longer distinguish between sucrose and sucralose. They now had an equivalent preference. Conversely, if she activated those neurons using some new experimental tools, she could switch an animal's preference to the artificial sweetener if it was linked to the activation of those neurons. This tells us pretty definitively that these neurons play some role in the sensing of sucrose but it doesn't actually tell us whether or not the glucose itself or the sucrose itself is actually being sensed by these neurons or by some other group of neurons, such as sweet sensors elsewhere in the body.

Chris - Where are these MCH neurons, and what, more importantly, perhaps do they connect to?

Jeffery - MCH neurons are present in a brain region known as the hypothalamus. In a particular region of the hypothalamus, known as the lateral hypothalamus, and this nucleus is generally thought to activate hunger. This particular hypothalamic region is intimately connected to reward circuits that play a role in changing the motivation for certain behaviours or certain preferences. And so, they're well positioned, both to sense glucose signals directly or indirectly and then connect them to reward circuits.

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