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Obesity can result in permanent brain damage

Food intake depends upon the integration of complex metabolic and neuronal signals between the brain and various organs, including the gut and nutritional signals in the blood. This network drives sensations of hunger and satiety, and regulates food intake and the motivation to search for food. 

Although these processes have been extensively studied in animals – including in the context of metabolic diseases such as obesity – studies on humans are lagging behind due to difficulties in designing experimental setups in clinics. 

How the research was conducted 

To address these limitations, a team of researchers led by the Amsterdam University Medical Centers and Yale University has recently designed a controlled trial which revealed that brain responses to specific nutrients are diminished in obese individuals and do not significantly improve even after weight loss. The study is published in the journal Nature Metabolism.

The scientists infused specific nutrients directly into the stomach of 30 participants with a healthy bodyweight and 30 obese participants, while measuring their brain activity through Magnetic Resonance Imaging (MRI) and levels of dopamine release through Single-Photon Emission Computed Tomography (SPECT) scans. 

What the researchers discovered 

The measurements revealed that, while the participants with a healthy body weight exhibited specific patterns of brain activity and dopamine release after nutrient infusion, in the participants suffering from obesity these responses were severely blunted.

“Our findings suggest that long-lasting brain adaptations occur in individuals with obesity, which could affect eating behavior. We found that those with obesity released less dopamine in an area of the brain important for the motivational aspect of food intake compared to people with a healthy body weight. Dopamine is involved in the rewarding feelings of food intake,” explained senior author Mireille Serlie, a professor of Endocrinology at Amsterdam UMC.

“The subjects with obesity also showed reduced responsivity in brain activity upon infusion of nutrients into the stomach. Overall, these findings suggest 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.”  

Moreover, ten percent body weight loss following a 12-week diet in obese participants did not seem sufficient to restore proper brain responses to nutrient intake, suggesting that long-lasting brain adaptations occur in obesity and remain even after weight loss is achieved. 

“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,” Serlie concluded.

Additional brain impacts of obesity 

Obesity has been found to have several potential effects on the brain, leading to both structural and functional changes.

Cognitive functioning

Numerous studies have shown that obesity can have a negative impact on cognitive functioning. This includes memory, attention, executive functions, and processing speed. For instance, obesity has been associated with poorer performance on tasks requiring executive functioning, which includes problem-solving, planning, and organization.

Brain structure

Obesity can also affect the physical structure of the brain. Neuroimaging studies have found differences in the brain structures of obese individuals compared to those of normal weight. These changes can include reduced white and gray matter volume and alterations in the connectivity of certain brain networks.

Alzheimer’s disease and dementia

Obesity, particularly mid-life obesity, has been found to increase the risk of Alzheimer’s disease and other forms of dementia later in life. This may be due, in part, to the impact of obesity on brain structure and function, as well as its association with cardiovascular risk factors.

Mental health

Obesity is associated with a higher risk of mental health disorders, such as depression and anxiety. The reasons behind this are complex and likely involve a combination of biological, psychological, and social factors. For instance, inflammatory processes associated with obesity might contribute to depression.

Inflammation and oxidative stress

Obesity is a state of chronic low-grade inflammation and is associated with increased oxidative stress. Both inflammation and oxidative stress are harmful to the brain and can contribute to neurodegenerative processes. For instance, they can damage neurons and alter signaling pathways within the brain.

Insulin resistance

Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. Insulin resistance has been associated with reduced cognitive performance and an increased risk of Alzheimer’s disease. This might be due to the fact that insulin plays an important role in many brain functions, including memory.

By Andrei Ionescu, Staff Writer

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