Why One Cream Cake Leads to Another

Continuously eating fatty foods perturbs communication between the gut and brain, which in turn perpetuates a bad diet.

By Ruth Williams | August 15, 2013

WIKIMEDIA, LOTUS HEADA chronic high-fat diet is thought to desensitize the brain to the feeling of satisfaction that one normally gets from a meal, causing a person to overeat in order to achieve the same high again. New research published today (August 15) in Science, however, suggests that this desensitization actually begins in the gut itself, where production of a satiety factor, which normally tells the brain to stop eating, becomes dialed down by the repeated intake of high-fat food.

“It’s really fantastic work,” said Paul Kenny, a professor of molecular therapeutics at The Scripps Research Institute in Jupiter, Florida, who was not involved in the study. “It could be a so-called missing link between gut and brain signaling, which has been something of a mystery.”

While pork belly, ice cream, and other high-fat foods produce an endorphin response in the brain when they hit the taste buds, according to Kenny, the gut also sends signals directly to the brain to control our feeding behavior. Indeed, mice nourished via gastric feeding tubes, which bypass the mouth, exhibit a surge in dopamine—a neurotransmitter promoting reinforcement in the brain’s reward circuitry—similar to that experienced by those eating normally.

This dopamine surge occurs in response to feeding in both mice and humans. But evidence suggests that dopamine signaling in the brain is deficient in obese people. Ivan de Araujo, a professor of psychiatry at the Yale School of Medicine, has now discovered that obese mice on a chronic high-fat diet also have a muted dopamine response when receiving fatty food via a direct tube to their stomachs.

To determine the nature of the dopamine-regulating signal emanating from the gut, Araujo and his team searched for possible candidates. “When you look at animals chronically exposed to high-fat foods, you see high levels of almost every circulating factor—leptin, insulin, triglycerides, glucose, et cetera,” he said. But one class of signaling molecule is suppressed. Of these, Araujo’s primary candidate was oleoylethanolamide. Not only is the factor produced by intestinal cells in response to food, he said, but during chronic high-fat exposure, “the suppression levels seemed to somehow match the suppression that we saw in dopamine release.”

Araujo confirmed oleoylethanol’s dopamine-regulating ability in mice by administering the factor via a catheter to the tissues surrounding their guts. “We discovered that by restoring the baseline level of [oleoylethanolamide] in the gut . . . the high-fat fed animals started having dopamine responses that were indistinguishable from their lean counterparts.”

The team also found that oleoylethanolamide’s effect on dopamine was transmitted via the vagus nerve, which runs between the brain and abdomen, and was dependent on its interaction with a transcription factor called PPAR-a.

Oleoylethanolamide levels are also reduced in fasting animals and increase in response to eating, communicating with the brain to stop further consumption once the belly is full. Indeed, oleoylethanolamide is a known satiety factor. Therefore, when chronic consumption of high-fat food diminishes its production, the satisfaction signal is not achieved, and the brain is essentially “blind to the presence of calories in the gut,” said Araujo, and thus demands more food.

It is not clear why a chronic high-fat diet suppresses the production of oleoylethanolamide. But once the vicious cycle starts, it is hard to break because the brain is receiving its information subconsciously, said Daniele Piomelli, a professor at the University of California, Irvine, and director of drug discovery and development at the Italian Institute of Technology in Genoa.

“We eat what we like, and we think we are conscious of what we like, but I think what this [paper] and others are indicating is that there is a deeper, darker side to liking—a side that we’re not aware of,” Piomelli said. “Because it is an innate drive, you can not control it.” Put another way, even if you could trick your taste buds into enjoying low-fat yogurt, you’re unlikely to trick your gut.

The good news, however, is that “there is no permanent impairment in the [animals’] dopamine levels,” Araujo said. This suggests that if drugs could be designed to regulate the oleoylethanolamide–to-PPAR-a pathway in the gut, Kenny added, it could have “a huge impact on people’s ability to control their appetite.”

L.A. Tellez et al., “A gut lipid messenger links excess dietary fat to dopamine deficiency,” Science, 341:800-02, 2013.

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Avatar of: D. Lane

D. Lane

Posts: 1

August 16, 2013

Another article demonizing fat.

Based on my own n=1 experience, fat is satiating.

It's the sugar that causes the cravings for more, more, more.

Avatar of: Neurona


Posts: 73

August 16, 2013

This appears to be very elegant work. For a few years now, I have taught my physiology students that, in the GI tract, "there are tongues in more places than just your mouth".  

Fat is indeed satiating, but overstimulating receptors with ligands leads to receptor downregulation, and the vicious cycle begins. It's all in the amount...

Avatar of: steveH


Posts: 1

August 17, 2013

Which part of this study showed that mice suffering from this deficiency actually over-ate? And how are we linking foods such as cake and ice cream to foods such as butter and beef based off of this? After all, that is how its being portrayed in the media here, now. I have been eating high-fat diets for years now and my increases and decreases in weight have nothing to do with the amount of fat in my diet, it remains about 30-40% of my calories both when I am gaining and when I am losing. Sounds like this study does a good job of evaluating dopamine deficiency, but that is far from proving "why one cream cake leads to another".

Avatar of: paleohumanz


Posts: 1

August 18, 2013

Reminds me on a recent trip to the library where I looked at sever "diet" books just to see the silliness they try to feed people. In this particular book their example: "Potato chips are a high fat food and easily over eaten" well, duh. Its actually a high carb food as well and not only that, it is a high carb food that drastically influences insulin levels (a rise of course). It is also perposterious to do a study on mice and compair it to human biology. Mice in nature would never eat a high fat diet so of course their responce to fat may be greater than that of humans, since we evolved eating plenty of fats from small game and insects.


August 21, 2013

Have 100 g carbohydrates, that's enough energy for four hours. The blood glucose level will rise immediately which increases the insulin level that stops fat metabolism.

There will be an excess of AcCoA and the liver will polymerize AcCoA to stearic acid (fat) that will be stored in fat cells. Then 50 g glucose is used up converted to ten g fat. After two hours the remaining 50 g glucose is usedd up as fuel, the blood glucose level will plummet craving anothe 100 g carbohydrates for the next 2 hours energy supply while another 10 g fas is stored.

The person has overeaten 100 g carbohydrates and stored another 20 g fat

Any fat in the cream cake will immediately be stored in the fat tissue as well.

Have 44 g fat instead and that's enough for four + hours of satisfaction.

No change in blood glucose level and thus no increased insulin excretion, no fat deposit.

No risk of "overeating"

This is physiology 101, biochemistry 101 and endocrinology 101.

Stop eating more than 100 g carbohydrates per day and the obesity and diabetes epidemics will cease.

Avatar of: Ebba


Posts: 1

October 26, 2013

Brand new mechanism involved in regulation of hunger signals in humans proposed in a Nature Commpunications paper published yesterday. The researchers describe the role of autoantibodies acting as carriers for the hormone ghrelin


Avatar of: Tigerite


Posts: 1

Replied to a comment from Björn Hammarskjöld made on August 21, 2013

November 8, 2013

There's also the factor that we're not mice, but human beings. It's all conjecture at this point.

Avatar of: kandi


Posts: 3

January 23, 2015

Since childbirth we sometimes experience neglect. As we grow older that might worsten or better. However, when we are given the freedom of choosing our food we will not control the things our taste buds enjoy better. Since the brain releases  endorphin which makes us feel in a state of extacy we like the feeling and loose control of when to stop indulging the unhealthy diet.



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