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October 17, 2008

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It's important to note that dopaminergic "satisfaction" is only one aspect of overeating - there's the feeling of satiety mediated by the neuropeptide cholecystokinin (CKK), which works on CKK receptors; the hormone leptin, which works in hypothalamus; other serotonergic hormones; neuropeptide Y (NPY); agouti-related peptide (AGRP); insulin sensitivity, which can also affect appetite...the list goes on.

Furthermore, overeating is only one factor that can contribute to obesity. It's important to not overlook energy expenditure, physical activity, lifestyle, etc.

Genetics may certainly underlie many (or even all) of the above factors, but lifestyle certainly plays a major role as well.

It’s amazing to see how even tiny receptors can play a pivotal role in how much we eat. I’m curious though about how other factors that other researchers have touched on might also be at play. In other words, is an obese person likely to just have one “faulty” mechanism such as this gene? Or is it more likely that a combination of things has gone awry – such as an emotional/behavioral response, a lack of exercise, a screwy metabolism and so on? It would be interesting and helpful to hear different experts chime in on this and how it can help overweight people gain control of their eating habits.

Chowder, you bring up a good point. No matter the underlying genetic factors that are involved, your lifestyle definitely plays a big role. Obesity is the result of large imbalances between the calories consumed and the calories burned. Although research like this is very important, it is equally critical to stress the need for exercise and a healthy diet to truly take a step forward in this obesity epidemic we are facing.

I think it's pretty cool that so many things that we do are connected to the reward systems in the brain! I do wonder how strong the reward systems in the brain are. For example, are food cravings in some people as strong as an addiction to drugs? This seems to make sense because so many people get caught in bad eating habits and sometimes are called "emotional eaters." This study seems to support the notion that emotional eating is not as far-fetched as some view it to be.

According to a review in the Journal of Neuroscience, the dorsal striatum may be so influential in decision making because of its interconnected network between the reward, motor, sensory and emotional systems. Since the dorsal striatum is involved in different processes of the brain, it is instrumental in initiating reactions. This could be a possible explanation as to why the compulsion to over-eat can be so powerful. The article can be found at http://www.jneurosci.org/cgi/reprint/27/31/8161

The study found that having less active striata was linked to an increased risk of becoming overweight, especially if they had the TaqIA gene. So the cause of obesity is linked to genetics rather than the habit of overeating? Regardless of what contributes to being obese -- overeating or genetic factors -- I think a healthy lifestyle that includes being physically active and eating smaller portions will definitely help prevent obesity.

I have some friends who work graveyard shifts and report cravings for comfort food. I think the reward pathways have something to do with this, as this story has alluded to. Maybe working a graveyard shift has something to do with the amount of dopamine. Why does working graveyard shifts, or simply being exhausted, make greasy, unhealthy foods more satisfying? Could it be of a similar mechanism to obesity and less satisfaction while eating?

I agree with Chowder that genetics is not the only factor that contributes to obesity. Lifestyle, such as type of diet and level of physical activity, plays a major role.

I thought this was very interesting. I was not aware of the Tag1A gene and that it's linked to less dopamine than the average person. Dopamine is a brain chemical that has been associated with cocaine use. Alcohol and drugs may also play a role in obesity.

Obese people may have less dopamine receptors, which are neurotransmitters that help produce feelings of satisfaction. Obese people may try to eat more to stimulate the dopamine “pleasure” circuits in the brain, just as addicts do by taking drugs. Strategies aimed at improving dopamine function might benefit in the treatment of obese individuals. Eating, like the use of and addictive drug, is a highly reinforcing behavior and induces pleasure. Obese people may have abnormalities in brain dopamine activity.

Studies have shown that "four regions of the brain and four neurotransmitters are a major part of the neurological reward pathway.” Dopamine has been said to be the “primary neurotransmitter of reward” and without sufficient amounts, it can lead to what has been termed “reward deficiency syndrome.” It has been stated that the reward system begins with one of the four neurotransmitters spreading out to the network and initiating a cascade, which results in a person feeling secure, calm and satisfied (the reward).

Research also shows that a significant amount of human behavior is aimed toward achieving these feelings. “Reward deficiency syndrome” occurs when the “networking” does not occur; for example, if dopamine is deficient. This study notes that the genetic abnormality of the allele 1 polymorphism results in fewer D2 receptors. This in turn leads to lower levels of dopamine-related activity in the brain, which can cause a disruption of the cascading function, resulting in feelings opposite a “reward." As a result, a person may feel the need to consume more food in an attempt to feel the “reward." This may contribute to obesity.

I agree that many other factors are involved in the development of obesity, but I feel the results of this study are worthy of future research in hopes of identifying any possible recommendations to fight this significant health issue.

Science Daily (Oct. 17, 2008) — Using brain imaging and chocolate milkshakes, scientists have found that women with weakened "reward circuitry" in their brains are at increased risk of weight gain over time and potential obesity. The risk increases even more for women who also have a gene associated with compromised dopamine signaling in the brain.

This information comes as no surprise to me. Preventing the re-uptake of dopamine at the synapse is the mechanism of action for amphetamines, which have been used as an unlabeled treatment for obesity. This allows more dopamine to be present in the synapse, allowing more stimulation of dopamine receptors and increased pleasure while eating.

Perhaps this study on the TaqIA gene maybe related to the growing epidemic of obesity in young adults in the United States. This provides a more physiological explanation of the obesity epidemic -- not just a behavioral/social one such as large fast food consumption. It’s unfortunate that some adults maybe genetically predisposed to obesity due to the lack of dopamine. The reward pathways of the brain are not only stimulated during eating, but they're also related to many other pleasurable activities such as sex and smoking.

This is an interesting finding, especially in terms of what it could translate into for pharmaceutical companies. I completely agree that in order to combat obesity, a healthy lifestyle is essential. But drugs that increase dopamine concentrations in the brain may also help limit obesity. There are many medications currently available to increase dopamine concentrations in the brain (they are used for Parkinson's disease), and I wonder if pharmaceutical companies will encourage more studies (or conduct studies themselves) to explore this obesity-dopamine link. I can only imagine what a positive finding would mean for their bottom-line.

This makes me think of the “nature vs. nurture” debate. It would be interesting to examine the TaqIA gene mutation in combination with eating habits during youth. For example, my mother did not give me and my sister candy when we were little, and McDonald's was for very special occasions only. Now that we are grown up, we are both slim (although many of our relatives are not). I wonder how much has to do with genetics in our situation.

This also makes me think of how some schools are starting to ban soft drinks and really unhealthy food for sale in their cafeterias, which could really impact life-long eating habits, regardless of genetic predispositions.

This study found a very important link for gene therapy, I think. It is a break for these predisposed obese people since they can have their problem fixed once, rather than having to take drugs daily to help them lose the unwanted weight.

I agree with Jill’s comment regarding "nature vs. nurture." Not to discount the genetic component of obesity, but blaming your genes and not leading a healthy lifestyle is an excuse. This genetic component can help us understand why certain individuals, despite eating well and exercising, can’t seem to lose weight. It may also help us understand why in depression patients, some patients have a tendency to overeat. It is important that the "marketing" of such studies is done carefully. We are not saying that genetics endorse overeating.

I agree with JF; the nature vs. nurture issue is definitely present here. Genetic predisposition is only part of the obesity issue. The fact is that in the current economic crisis, where many companies are beginning to loose money, McDonald's is one of the few that is seeing higher profits. Americans simply need to stop going to drive-thru fast-food restaurants so often and focus more on the joy of creating meals and sitting down with the family and teaching these values to our children.

I would like to address some of the prior comments: Max suggested that this study showed that genetics is responsible for weight-gain rather than over-eating. However, this is not the case. This study is presenting a possible reason that some of us eat more than we need to, not that people with less dopamine response eat less.

Jane talked about a link between exhaustion and over-eating. Perhaps this does have something to do with a need to increase dopamine levels. Dopamine is a precursor of norepinephrine and epinephrine, which are associated with wakefulness, so it is possible that the reward we get from eating comfort foods could also lead to the production of these stimulating hormones.

Finally, Linda suggested that amphetamines work as appetite suppressants by increasing the pleasure of eating – generally if we like how something makes us feel we want to do it more, not less.

Did they find in this study that the obese patients had lower levels of dopamine? And if so, does that mean we can replete dopamine, for lack of better words, as one would with a patient with Parkinson’s by giving a form of dopamine that would reach the CNS such as methyldopa?

It becomes a real challenge to fight our natural instincts. Our ancestors of many millennia probably developed this brain chemistry to increase our food intake as a means of survival. Now in our modern world, our instincts are making some of us obese. A new spin on survival of the fittest!

While I realize this study may be part of a process necessary to confirm the activity and association of the TaqIA gene, more must be done to include viable controls. It is likely for teenage girls and women ages 18-22 to gain weight. The link between the TaqIA gene and obesity is weak without a proper control.

Many studies have shown that blocking the effects of dopamine can lead to increased appetite in obese people. According to this study, obese people with less active strata have a higher risk of obesity. What
would be the best choice for these people? Having drug treatments that reverse this dopamine problem and changing behavioral patterns like eating a balanced diet with an appropriate number of calories, exercises, etc. I think people suffering this epidemic disease need more reliable information about obesity causes, gene factors, preventive methods and treatments.

I wonder why only women and teenage girls were studied. Is it because obesity only affects female? If this is true, then I think the pharmaceutical industry hit a jackpot in regard to developing a new drug that targets only female population. Physical appearance, as I see it, is everything to women.

Iris, obesity affects men and women, adults and children. I think the prevalence for men and women differ only slightly by ~1% or so. I also have to comment that physical appearance is just as important to men as it is to women. Just think of all the aging men who worry about hair loss and the many Rogaine® commercials!

Scientists have found that the cravings people experience with food is also caused by the same brain chemical (called dopamine) that makes an addict crave drugs. By letting a food-deprived person even smell food causes a significant elevation in brain dopamine.

People who are missing the TaqIA gene have to compensate with more food in order to feel the pleasure that people with that gene feel instantly with food and know when to stop eating.

Is there anything you can take to increase dopamine if you have the TaqIA gene?

It is interesting to see that research on genetic factors like TaqIA is being done to explain obesity. It seems as though we are trying to find an excuse or an underlying reason why people are obese when there are clearly other reasons. I think eating habits and inactivity are the sole causes of obesity, and while gentic factors may play a role, it is not the cause.

It’s important to remember that obesity is linked to many factors, not just the dopaminergic system. Meaning, it may be due to the satiety center in the brain, one’s lifestyle, metabolic issues and even genetic predispositions. Also, individuals may become obese if there is an imbalance between the calories consumed and the calories burned. If not enough calories are burned, relative to what is consumed, the excess calories can be stored as fat. I strongly believe that as long as a person remains physically active, he can eat whatever he wants. If a person has Taq/A gene, does this mean he is also less likely to become addicted to nicotine?
Natasha

This is an interesting study. I do question if every factor was analyzed while this study was conducted. For instance, was it monitored how long each subject took to consume their milkshakes or other food items? The amount of time one spends ingesting a certain food item has been known to correlate with the amount of pleasure felt, or amount of dopamine released during consumption. Many weight-loss specialists recommend people who are trying to change their eating habits to eat slower, chew more and mentally engage themselves while they eat. Enjoying the food and eating slower has also been shown to produce a fuller effect sooner, as gastric stretch takes almost 20 minutes to produce a "full" feeling.

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