How obesity affects the brain’s ability to sense and respond to nutrients in the stomach and blood


In this blog post, I will write a very detailed article based on a recent study published in Nature Metabolism on June 12, 2023.

The study is titled “Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study” and was conducted by a team of researchers from Amsterdam UMC, Yale University and other institutions.

The study aimed to investigate how obesity affects the brain’s ability to sense and respond to nutrients in the stomach and blood, and whether these effects are reversible after weight loss.

The study involved 30 participants with a healthy body weight and 30 participants with obesity, who underwent two imaging sessions: one before and one after 10% diet-induced weight loss. In each session, they received intragastric infusions of glucose, lipid or water (as a control) while their brain activity was measured by functional magnetic resonance imaging (fMRI) and their striatal dopamine release was measured by single-photon emission computed tomography (SPECT). The researchers also assessed their plasma hormones and glucose levels, hunger scores and caloric intake.

The results showed that participants with a healthy body weight had nutrient-specific and preference-independent brain responses to glucose and lipid infusions, indicating that they could sense and react to the caloric value of nutrients independently of their taste.

These brain responses involved increased activity in regions related to reward, motivation, memory and cognitive control, as well as increased dopamine release in the striatum, a key area for reward processing. In contrast, participants with obesity had severely impaired brain responses to both glucose and lipid infusions, showing reduced activity and dopamine release in these regions.

These impairments were not restored after weight loss, suggesting that obesity causes long-lasting changes in the brain that affect its sensitivity to nutritional signals.

The researchers concluded that obesity impairs the brain’s ability to regulate eating behavior by reducing its responsiveness to post-ingestive nutrient signals. They suggested that these impairments may contribute to overeating and weight gain, as well as to the difficulty of maintaining weight loss after successful dieting. They also highlighted the need for further research to understand the mechanisms underlying these brain adaptations and to develop strategies to prevent or reverse them.

This study is one of the first to demonstrate how obesity affects the brain’s response to nutrients in humans using a combination of imaging techniques and intragastric infusions.

It provides novel insights into the neural basis of eating behavior and its dysregulation in obesity. It also has important implications for the prevention and treatment of obesity and its related complications.

in deep …

Obesity and Functional and Structural Brain Changes

Changes in brain volume and density are often reported as measures of structural brain changes. These structural changes have been reported in obese populations, especially in elderly people, and growing evidence suggests that obesity is associated with regional structural alterations [33].

A tensor-based morphometry study [34] of cognitively healthy obese older individuals reported a reduced volume in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus. Similarly, high BMI has been negatively associated with the integrity of the frontal lobes in middle-aged adults [35] and the elderly [36]. In addition, obesity has been associated with global brain structural change, for example, overall cerebral atrophy in grey matter and white matter volume [34].

Yau et al., (2014) [37] detected signs of cortical thinning in specific brain regions and reduced microstructural integrity in white matter tracts in obese adolescents, and associated overall lower academic performance with structural impairments, but obese youths performed no worse than non-obese youths in cognitive tests in this study.

While associations between brain structural alterations and cognitive performance cannot inform causality, smaller sizes and volumes indicate neuronal loss, and therefore it is biologically plausible to link these changes to poor cognitive performance.

However, why brain structural changes did not determine poor cognitive outcomes in this study is unclear. Perhaps changes in the brain become evident in obese adolescents, but the impact of these changes on cognition are not manifested until later in life. This puzzle may be explored using advanced brain imaging techniques that are more likely to detect structural micro-changes that are not translated into immediate cognitive deficits in early stages of decline. Therefore, it is worthwhile combining physiological assessment with cognitive assessments to explore the impact of obesity on brain function.

Opstal et al., (2019) [38] examined the impact of weight loss (prolonged fasting) on brain activity in obese people. This study included 14 participants (two men) who were categorised as obese by BMI. Brain imaging data were collected after an overnight fast, a 48 h fast and an 8 week intervention for weight loss using whole-brain resting-state functional magnetic resonance imaging (MRI).

The authors reported that the weight loss intervention decreased activation in the parts of the brain involved in salience, sensory motor, and executive control, suggesting a relationship between obesity-related changes in neurological activity and weight loss. Recently, a study by Opel et al., 2020 [39] conducted a mega-analysis investigating brain structure abnormalities and obesity and also considered the effect factors of age, genetic risk, and psychiatric disorders.

This study examined the relationship between obesity (BMI > 30 kg/m2) and brain structure involving in 6420 participants. Findings revealed that obesity was significantly associated with cortical and subcortical abnormalities independently, especially in lower temporo-frontal cortical thickness. A higher polygenic risk score and age played an interaction role in cortical thickness.

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