Children with obesity, who have recently lost weight, are more likely to show hunger-related activity in their brains after a meal, according to research presented today at the 60th Annual European Society for Paediatric Endocrinology Meeting. This brain activity, reflecting that they were unsatisfied by their meal, happens even though their gut hormone levels have changed, as expected, to reduce hunger and indicate fullness. This disconnect between food satisfaction in their brain versus their digestive system may underlie why many people regain weight, particularly after a strict diet. Understanding and addressing this persistence of hunger-promoting brain activity could lead to better and more sustainable treatments for obesity in children and adults.
Obesity is a growing worldwide health crisis with an estimated 124 million children affected globally. Obesity increases the risk of many other health problems including type 2 diabetes, heart disease and cancer. Obesity in children is often managed through family-based behavioural therapy involving regular outpatient sessions that focus on dietary and physical activity education. In the USA, the gold standard for such programmes is a minimum of 26 contact hours over a 6 month period, however, many children regain weight soon after programme completion. It is poorly understood why the success rate is so low. Appetite and metabolism, and therefore weight gain, is regulated by activity in both the brain and the digestive system. Understanding how these processes are affected by weight loss may help us better understand the mechanisms that predispose children to rebound weight gain.
In this study, Professor Roth and colleagues at Seattle Children’s Hospital in the USA, compared brain appetite regulation activity with gut hormone responses in children with obesity before and after a 24-week weight loss programme. Using functional MRI, they assessed activation patterns in appetite-regulating brain areas in response to high- vs. low-calorie images, after a meal. Gut hormone levels were also assessed before and after meals, at the beginning and end of the programme. At the end of the programme, children still showed high levels of activation in brain areas related to appetite, after a meal, in response to food images, indicating that they were hungry. However, their levels of appetite-regulating gut hormones indicated fullness and satiety. Strikingly, the children who lost the most weight, showed the strongest activation in their brains to food cues after a meal, at the end of the programme.
Professor Roth comments, “Our results imply that during weight loss intervention, your body acts to conserve fat through maintaining hunger responses in the brain, and that this needs to be addressed, perhaps through drug treatment, for successful and sustained weight loss in children with obesity.”
Although Professor Roth cautions, “These findings are from a small group of children tested only at the start and end of the intervention programme, so larger and more detailed studies would be needed to confirm this central effect. It would also be useful to investigate how long the disconnect between central and local appetite regulation persists after maintained weight loss, to guide intervention plans.”
Professor Roth suggests, “For more successful treatment of obesity in children, we should avoid interventions that lead to fast body weight reductions and instead aim for more gradual and consistent lifestyle changes, over years rather than months, which will lead to sustained and long-term improvements in weight loss and health.”
Impaired Brain Satiety Responses by Functional Neuroimaging After Weight Loss Therapy in Children with Obesity
Christian Roth1, Susan Melhorn2, Mary DeLeon2, Maya Rowland1, Clinton Elfers1, Alyssa Huang3, Brian Saelens1, Ellen Schur2
1Seattle Children's Research Institute, Seattle, USA. 2University of Washington, Dept. of Medicine, Seattle, USA. 3Seattle children's Hospital, Seattle, USA
Background: Obesity interventions often result in increased motivation to eat after weight loss.
Objective: We investigated relationships between obesity outcomes and changes in brain activation by visual food cues and hormone levels in response to obesity intervention by family-based behavioral treatment (FBT).
Design, Methods, and Participants: Functional neuroimaging and plasma hormone assessments before and after 24-week FBT intervention in children with obesity (OB, n=28), or children of healthy weight without intervention (HW, n=17), all 9-11-year-old males and females.
Main Outcome Measure(s): Evaluation of meal-induced changes in neural activation in response to viewing high- vs. low-calorie food cues across appetite-processing brain regions and gut hormones.
Results: Among children with OB who underwent FBT, greater declines of BMI z-score were associated with less reductions after the FBT intervention in meal-induced changes in neural activation to high- vs. low-calorie food cues across appetite-processing brain regions (p<0.05), and the slope of relationship was significantly different compared to children of HW. In children with OB, less reduction in brain responses to a meal from before to after FBT was associated with greater meal-induced reduction in ghrelin and increased meal-induced stimulation in peptide YY and glucagon-like peptide-1 (all p<0.05). Furthermore, a greater reduction of BMI z-score was associated with a greater reduction of free leptin index and increase of the adiponectin to leptin ratio (all p<0.01), indicating an increase in leptin sensitivity. After FBT, an increased buffet meal intake was associated with higher leptin levels (p<0.05).
Conclusions: In response to FBT, adaptations of central satiety responses and peripheral satiety-regulating hormones were noted. After weight loss, changes of peripheral hormone secretion support weight loss, but there was a weaker central satiety response. The findings suggest that even when peripheral satiety responses by gut hormones are intact, the central regulation of satiety is disturbed in children with OB who significantly improve their weight status during FBT, which could favor future weight regain.