“I do not feel full even after I eat” is what I heard from so many of my patients. Even after bariatric surgery, this feeling of fullness would go away initially but then it would come back, and they found themselves again overindulging. Why does this happen? Brain studies have shown that obesity impairs the dopamine signaling in the brain that tells the brain it is satisfied after nutrients enter the stomach. This was found to be normal in healthy-weight people but abnormal in people with obesity. Some say it is obesity that causes brain adaptations to alter the signaling. I feel like it is the genes that cause the brain to reconfigure over time, which is why people become obese. So what happened first, the chick or the egg? Did obesity cause the brain to change, or was it predestined due to genetics?
Some people have a gene along the dopamine pathway that does not allow for normal dopamine release in response to things that typically would increase dopamine, including food. Studies have shown that specifically dopamine receptor D4 gene regulates multiple cognitive functions with potential relevance for eating behavior and, thereby, body weight, including behavioral inhibition and flexibility, and motivation and reward processing. Human studies have found that diminished dopamine inhibitory feedback in DRD4-7R carriers is linked to weaker physiological dopamine signaling than non-carriers. People with this genetic deficiency do not feel “the high” as easily or at all compared to people with no alterations in this gene, which can lead to addictive behavior, food, or other vices. And studies show that the lower DRD4 expression in the pre-frontal cortex was associated with greater food intake in the satiated state among children in the context of lower socioeconomic status.
People overeat because their brain does not get the dopamine signal of having nutrients and being satisfied. This is due to both the brain and a person’s genetics; we now know it is not due to a lack of motivation or self-control. Studies also have shown that 10 percent weight loss still has not resolved this, so this may be why after weight loss people regain. So the reason you overeat is not due to a lack of self-control.
As a bariatric surgeon, I am not convinced that surgery will fix this genetic mutation. Although my previous work showed that surgery can have an epigenetic effect and change gene expression by methylation, I am unsure if it changes this gene. I have noticed clinically that these newer once-a-week GLP-1 medications have been able to affect this signaling, so people have been “able to feel full” and understand what that truly is.
Franchell Hamilton is a bariatric surgeon.