Periodic Reporting for period 2 - OBESITY_SPIRAL (The obesity spiral: inflammation and effortless fast food choices)
Reporting period: 2022-05-01 to 2023-10-31
Obesity is a major threat to human health, often characterized by increased consumption of energy-dense and easy-to-eat, ‘effortless fast food’. In everyday life, we have to decide whether it is worth exerting effort to obtain rewards. The willingness to invest effort to obtain rewards (such as food) can also be measured in the lab. However, it is yet unclear whether obesity is associated with effort avoidance or rather with enhanced willingness to exert effort for (food) reward, with conflicting results in both rodent and human studies.
A factor that might explain these mixed findings is inflammation. Approximately half of individuals with obesity suffer from chronic increases in low-grade, systemic inflammation due to excess body fat. As you might recognize from being sick, inflammation during sickness also results in different behaviour, i.e. characterized by fatigue, anhedonia, depression, and apathy. Interestingly, lab studies that have acutely manipulated inflammation find that inflammation specifically affects effort expenditure, leaving reward processing unaffected. Animal studies found that these effects of inflammation on effortful behaviour depend on dopamine levels in the brain. Indeed, in human studies dopamine-rich brain regions are also most affected by inflammation manipulations.
Obesity-associated inflammation might explain low effort, high reward ‘fast food’ choices, via affecting brain dopamine levels; with excess of ‘fast food’ nutrients further worsening inflammatory tone, leading to a negative obesity spiral. However, the link between inflammation and effortful behaviour has never been studied in obesity. A better understanding of cost-benefit decision-making in obesity is of crucial importance to better explain why lifestyle changes to lose weight are so hard to maintain for the majority of individuals with an unhealthy weight.
Here, I will test the roles of inflammation and dopamine in effort-based decision making in obesity by employing task-based functional magnetic resonance imaging (fMRI), neurochemistry and measures of daily life decisions in combination with blood inflammatory markers. Using an anti-inflammatory intervention and dopamine manipulations, we will elucidate the crucial factors of the obesity spiral.
A factor that might explain these mixed findings is inflammation. Approximately half of individuals with obesity suffer from chronic increases in low-grade, systemic inflammation due to excess body fat. As you might recognize from being sick, inflammation during sickness also results in different behaviour, i.e. characterized by fatigue, anhedonia, depression, and apathy. Interestingly, lab studies that have acutely manipulated inflammation find that inflammation specifically affects effort expenditure, leaving reward processing unaffected. Animal studies found that these effects of inflammation on effortful behaviour depend on dopamine levels in the brain. Indeed, in human studies dopamine-rich brain regions are also most affected by inflammation manipulations.
Obesity-associated inflammation might explain low effort, high reward ‘fast food’ choices, via affecting brain dopamine levels; with excess of ‘fast food’ nutrients further worsening inflammatory tone, leading to a negative obesity spiral. However, the link between inflammation and effortful behaviour has never been studied in obesity. A better understanding of cost-benefit decision-making in obesity is of crucial importance to better explain why lifestyle changes to lose weight are so hard to maintain for the majority of individuals with an unhealthy weight.
Here, I will test the roles of inflammation and dopamine in effort-based decision making in obesity by employing task-based functional magnetic resonance imaging (fMRI), neurochemistry and measures of daily life decisions in combination with blood inflammatory markers. Using an anti-inflammatory intervention and dopamine manipulations, we will elucidate the crucial factors of the obesity spiral.
We have developed innovative ways of studying effort-based decision making in obesity, with an increasing level of ecological validity: a novel, mechanistic cognitive paradigm to probe effort and reward regions during brain scanning (fMRI), a novel food intake test in the lab, a novel experience sampling method for measuring daily life (active) behaviour. Together with state-of-the-art measures of (neuro)inflammation based on blood and MRI measures, we are now testing and analysing the inflammation-effort link in a large sample of women with overweight/obesity. Individuals with low-grade, systemic inflammation are invited to additionally participate in a 3-month anti-inflammatory drug study (vs. placebo) with a repetition of all measures post-intervention.
In the meantime, we set up a large online study (n= 418) with a similar decision-making task as the above-mentioned fMRI task, to investigate how an inflammatory event, i.e. a current or past COVID-19 infection, affects effort and reward sensitivity and whether an increased body-mass index (BMI) is a predictor for the effects. As predicted, both higher self-reported fatigue and BMI were associated with effort avoidance, not with reward sensitivity. This shows the sensitivity of the effort-based decision-making task as well as the importance of being able to separate effort from reward sensitivity, which has not yet been done in obesity research.
In the meantime, we set up a large online study (n= 418) with a similar decision-making task as the above-mentioned fMRI task, to investigate how an inflammatory event, i.e. a current or past COVID-19 infection, affects effort and reward sensitivity and whether an increased body-mass index (BMI) is a predictor for the effects. As predicted, both higher self-reported fatigue and BMI were associated with effort avoidance, not with reward sensitivity. This shows the sensitivity of the effort-based decision-making task as well as the importance of being able to separate effort from reward sensitivity, which has not yet been done in obesity research.
This project is the first to investigate whether a chronically elevated inflammatory tone - as a direct result of excess body fat – might explain inconsistent findings about motivation to exert effort for food reward in obesity, and the crucial role of brain dopamine. Specifically, obesity is usually defined in terms of BMI, but BMI does not map directly onto inflammatory tone, which is more selectively related to fat storage in certain parts of the body. This is relevant as finding the motivation/effort to change eating habits seems only possible for a small minority of people with obesity, given the low percentage (2-20%) with successful long-term weight loss using lifestyle changes. If the novel obesity-spiral hypothesis can be validated, then individual success in maintaining weight loss by healthy food choices might be determined by biological, inflammatory markers. As such, studying the inflammation-effort link in individuals with obesity might both help in de-stigmatizing obesity and in finding treatment options to face the obesity challenge.
In addition, the proposed research is relevant outside the field of obesity. Effort-related aspects of motivation are associated with symptoms such as apathy, fatigue, and psychomotor slowing, which cross multiple neuropsychiatric disorders, including depression, schizophrenia, and Parkinson’s disease. These disorders are also characterized by an elevated inflammatory tone, but with a different source than the inflamed fat tissue seen in obesity. The currently proposed transdiagnostic neurobiological focus may ultimately lead to personalized/precision medicine—identifying the right treatment for an individual based on their neurobiological and behavioural phenotype, which may cross multiple pathologies.
In addition, the proposed research is relevant outside the field of obesity. Effort-related aspects of motivation are associated with symptoms such as apathy, fatigue, and psychomotor slowing, which cross multiple neuropsychiatric disorders, including depression, schizophrenia, and Parkinson’s disease. These disorders are also characterized by an elevated inflammatory tone, but with a different source than the inflamed fat tissue seen in obesity. The currently proposed transdiagnostic neurobiological focus may ultimately lead to personalized/precision medicine—identifying the right treatment for an individual based on their neurobiological and behavioural phenotype, which may cross multiple pathologies.