The obesity spiral: inflammation and effortless fast food choices

ongoing

Obesity is a major threat to human health, often characterized by increased consumption of energy-dense and easy-to-eat, ‘effortless fast food’. A better understanding of effort-related motivation in obesity is important to explain why healthy lifestyle changes are often so hard to maintain. Previously, I have demonstrated the neurocognitive and neurochemical processes underlying motivational control of behaviour. However, in obesity, findings about the motivation to overcome effort costs for food reward – and associated dopamine signalling - are inconsistent, suggesting another – yet unknown - variable. Here, I am the first to suggest that this variable is chronic low-grade inflammation - as a direct result of excess body fat. Peripheral inflammation can affect the brain dopamine system to decrease effortful behaviour, enforcing the downwards spiral of obesity. However, how an elevated inflammatory tone in obesity relates to effort-based decision-making is currently unknown. Here, I aim to elucidate the neurocognitive mechanisms underlying effort-based decision-making in human obesity and the explanatory role of inflammation, using both an observational and a supplementation design with the anti-inflammatory aspirin-like drug salsalate. Moreover, I will determine the causal role of dopamine in effort-based decision-making in obesity by employing acute administration of the dopamine precursor levodopa, and I will study levodopa’s effects as a function of inflammatory tone. I will develop a novel fMRI paradigm that dissociates food reward anticipation, reward sensitivity versus effort avoidance during effort decision, effort exertion and reward consumption. Lab findings will be translated to real life with experience sampling methods. This innovative, interdisciplinary approach will elucidate the inflammation-effort link in obesity and explain inconsistent findings about dopamine abnormalities and effortful behaviour in obesity.