A new study reveals the real reason “why most people regain weight after initially successful weight loss.” Don’t blame your diet, daily habits, or genes.

The study, just published in Nature Metabolism, found that the brains of overweight or obese people impair the brain’s response to nutrients – and this is why they “regain weight after initially successful weight loss.”

Brain responses to distinct nutrients are attenuated in those with obesity and do not show improvement even after shedding weight, as per new research conducted collaboratively by Amsterdam UMC and Yale University, which has been published in Nature Metabolism today.

Mireille Serlie, the chief investigator and a Professor of Endocrinology at Amsterdam UMC, elucidates that the study reveals the possibility of persistent neural adaptations in individuals grappling with obesity, which might have a significant bearing on their eating patterns.

According to the findings, individuals with obesity manifested a lesser release of dopamine within a specific brain region that is pivotal for the motivational aspect associated with food consumption, as opposed to those with a normal weight. Dopamine is a neurotransmitter that plays a key role in the gratification derived from consuming food.

Additionally, the study noted that participants with obesity exhibited diminished brain activity in response to the infusion of nutrients into their stomach.

Collectively, this points towards the possibility that “sensing of nutrients in the stomach and gut and/or of nutritional signals is reduced in obesity and this might have profound consequences for food intake.”

It’s essential to recognize that the ingestion of food is governed by a sophisticated interplay of metabolic and neuronal cues exchanged between the brain and several organs, including the gut, along with the signals related to nutrition present in the blood.

This intricate network is responsible for eliciting hunger and satiety sensations, modulating the intake of food, and influencing the motivation to seek food. While there is an evolving understanding of these processes in animal models, especially in the context of metabolic disorders like obesity, the knowledge regarding their operation in humans remains limited. This is, in part, attributed to the challenges in devising experimental setups in clinical settings which can offer insights into these mechanisms.

To bridge this knowledge gap, Serlie, who holds a professorship at Yale as well, in collaboration with her team from both institutions, designed a methodical experiment. The experiment encompassed infusing specific nutrients directly into the stomachs of two groups, each comprising 30 individuals – one with a healthy weight and the other with obesity – and concurrently monitoring their brain activity using MRI scans and assessing dopamine release through SPECT scans.

The data demonstrated that the participants with a healthy weight exhibited distinct patterns in brain activity and dopamine release post-nutrient infusion. In stark contrast, these responses were markedly suppressed in participants with obesity.

Interestingly, even a 10% reduction in body weight achieved through a 12-week dietary intervention failed to ameliorate these neural responses among individuals with obesity. This indicates that obesity instigates enduring changes in the brain, which continue to persist even once weight loss has been attained.

“The fact that these responses in the brain are not restored after weight loss, may explain why most people regain weight after initially successful weight loss,” remarks Serlie.  

Source: 10.1038/s42255-023-00816-9

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