Abstract
Significant scientific steps have been made in comprehending how the brain regulates food intake and how its disruptions lead to overeating and obesity. However, much of this understanding stems from rodent studies, necessitating translation to human contexts, especially amid the ongoing global obesity crisis. This thesis aimed to increase our understanding of food intake regulation physiology and the brain mechanisms underlying obesity in humans. It underscores obesity as a condition where the brain's control over food intake is compromised.
In Part 1, we delve into the pathogenesis of obesity. Chapter 2 reviews factors contributing to obesity including energy expenditure, neurotransmitters and regulatory brain circuits. Chapters 3 and 4 narrow down to serotonin and dopamine, emphasizing their implications in obesity pathophysiology.
In Part 2, we focus on cerebral responses to nutritional changes in lean individuals and those with obesity. In Chapters 5 and 6, we show the physiologic responses to intragastric glucose and lipid in several critical brain regions governing energy consumption. We found that these brain responses are largely missing in humans with obesity and do not change after diet-induced weight loss. In Chapter 7, we show that the hypothalamic serotonin system adapts to prolonged fasting in lean men, but not in men with obesity.
In Part 3, we explore behavioral traits and the brain dopamine system. In Chapter 8, we describe no correlation between food craving and striatal dopamine transporter availability. In Chapter 9, we provide the translation of the Yale Food Addiction Scale 2.0 and results of validation in Dutch-speaking populations.
Overall, the thesis elucidates obesity as a complex interplay of physiological, neurological, and behavioral factors, necessitating multifaceted approaches for effective intervention and management.
In Part 1, we delve into the pathogenesis of obesity. Chapter 2 reviews factors contributing to obesity including energy expenditure, neurotransmitters and regulatory brain circuits. Chapters 3 and 4 narrow down to serotonin and dopamine, emphasizing their implications in obesity pathophysiology.
In Part 2, we focus on cerebral responses to nutritional changes in lean individuals and those with obesity. In Chapters 5 and 6, we show the physiologic responses to intragastric glucose and lipid in several critical brain regions governing energy consumption. We found that these brain responses are largely missing in humans with obesity and do not change after diet-induced weight loss. In Chapter 7, we show that the hypothalamic serotonin system adapts to prolonged fasting in lean men, but not in men with obesity.
In Part 3, we explore behavioral traits and the brain dopamine system. In Chapter 8, we describe no correlation between food craving and striatal dopamine transporter availability. In Chapter 9, we provide the translation of the Yale Food Addiction Scale 2.0 and results of validation in Dutch-speaking populations.
Overall, the thesis elucidates obesity as a complex interplay of physiological, neurological, and behavioral factors, necessitating multifaceted approaches for effective intervention and management.
| Original language | English |
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| Award date | 28 Jun 2024 |
| Publication status | Published - 2024 |