New Study Demonstrates that Sugar has to be Palatable to be Fattening in Mice

Dr. Anthony Sclafani's research group just published a study definitively demonstrating that high palatability, or pleasantness of taste, is required for sugar to be fattening in mice (1).  Dr. John Glendinning was lead author. Dr. Sclafani's group has done a lot of excellent research over the years.  Among other things, he's the person who invented the most fattening rodent diet in the world-- the 'cafeteria diet'-- composed of human junk food. 

Mice and rats love sweet food and drinks, just like humans.  If you give them a choice between plain water and sugar water, they'll overconsume the sugar water and become obese.  I have argued, based on a large body of evidence, that the reward value and palatability* of these solutions are important to this process (2, 3, 4).  This is really just common sense honestly, because by definition if the solution weren't rewarding the mice wouldn't go out of their way to drink it instead of water, the same way people wouldn't go out of their way to get soda if it weren't rewarding.  But it's always best to confirm common sense with research.

This study didn't address reward in any case-- it was focused specifically on palatability.  In mice as in humans, sweet tastes are detected by special proteins on the tastebuds, and the signal is transmitted within the cell by another set of proteins, and the genes encoding these proteins are known.  Dr. Sclafani's group asked a simple question: "is sugar still able to make mice obese if they can't taste its sweetness?"  They did this by genetically "knocking out" two different proteins, one in each line of mice, that are required for the perception of sweetness on the tongue (5).

The investigators showed that mice lacking these proteins have a normal food intake and body fatness when fed standard lab chow, but unlike normal mice both mutant strains are almost completely resistant to fat gain when given a sugar solution.  This is despite the fact that they drank a similar amount of sugar as the normal mice, which became obese**.  Basically, they drank the sugar water but it was no longer fattening once it didn't taste sweet.

But here's the coup de grace.  To make sure the mice weren't just resistant to obesity in general for some reason that has nothing to do with palatability, they altered the sugar solutions by adding a very small amount of fat emulsion, so that the solutions were once again palatable to all groups of mice.  Now, suddenly, the mice that couldn't taste sweetness got just as fat on the sugar solution as normal mice! The paper's main conclusion:

Our results suggest that nutritive solutions must be highly palatable to cause carbohydrate-induced obesity in mice...

I couldn't imagine a better way to test this hypothesis, and even I wouldn't have expected such a striking outcome.  This study completely shuts down the argument-- never convincing to begin with-- that food palatability is not relevant to body fatness.  Consistent with a large body of evidence in animals and humans, it supports the prevailing view among obesity researchers that excessive food palatability is an important factor in the development of obesity.  It also supports the argument I made in my post "Is Sugar Fattening?", that added sugar can be fattening because it increases the energy density, palatability, and reward value of food, rather than due to a metabolic effect that occurs after ingestion. 


* Reward.  The brain contains a "reward" system, whose job it is to gauge the desirability of food (among other things) and reinforce and motivate behaviors that favor the acquisition of desirable food.  For example, if you eat a strong cheese for the first time, maybe it won't taste very good to you.  As it's digested, your reward system gets wind that it's full of calories however, and the next few times you eat it, it tastes better and better until you like the flavor.  This is called an acquired taste, and the reward system is what does the acquiring, motivating you to obtain a food it has deemed safe and desirable.  Eventually, you may go out of your way to purchase the cheese or beer at the grocery store because you like it so much, and maybe you'll consume cheese or beer even if you aren't hungry or thirsty.  This is an example of the reward system reinforcing and motivating behaviors related to foods that it considers desirable.  Processed "junk foods" such as ice cream, fast food, sweetened soda, cookies, cake, candy and deep fried foods are all archetypal hyper-rewarding foods. 

Palatability is a related concept-- it is simply the pleasantness of a food; how much a person enjoys eating it.  Palatability is determined in part by inborn preferences (e.g., a taste for sugar and energy dense foods), and in part by the reward system (acquired tastes).  Palatability is governed by the hedonic system in the brain, which is closely integrated with the reward system.

The reward system is what motivates you to get food and put it to your lips, every time you eat.  When scientists shut it down in mice, they completely cease eating (6).  The hedonic system influences how much you eat once you begin a meal-- highly palatable food generally increases food intake by activating this system (7).  Together, reward and hedonic circuitry in the brain determine in large part how often you eat, what you eat, and how much you eat, and this is influenced by the attributes of the food that's available.

** Basically, they still find the sugar solution rewarding, just not palatable.  It has been known for a while that sugar receptor knockout mice still find sugar rewarding.  It just takes them longer to develop that reward association, as Dr. Sclafani's paper demonstrated.  The post-ingestive effects of the sugar allow them to form a conditioned preference for the sugar bottle, and therefore seek it out and drink a bunch of it, despite the fact that it doesn't taste sweet to them.