Onderzoek naar voeding en de hersenen

Rationale: The worldwide obesity epidemic is a major health burden. Obesity is caused by disturbed feeding behaviour, leading to overconsumption of high-calorie and highly palatable food. Feeding behaviour is regulated by a complex interplay of the homeostatic and hedonic systems, and influenced by peripheral inputs. Recent evidence suggests that ingested nutrients trigger gut-to-brain signals that stimulate central (brain) dopamine release. Changes in post-ingestion nutrient signals may be involved in the development of the pathological (habitual/compulsive) feeding behaviour in obese humans. However, the mechanism of nutrient-triggered dopamine release and its potential role in obesity remain to be elucidated. Gaining more insight in post-ingestion nutrient signalling is necessary to develop new therapeutic options to restore disturbed feeding behaviour in obesity.

Objective: To study the effects of post-ingestion nutrients on brain activity and brain dopaminergic responses in lean subjects, and in obese subjects before and after diet-induced weight loss.

Study design: Single-blind randomized cross-over study

Study population: Lean (BMI 20-25 kg/m2) and obese (BMI >30 kg/m2) men and (postmenopausal) women aged 50-75 years (n = 30 per group)

Main study parameters/endpoints:

Differences in brain fMRI signal and differences in striatal dopamine release (measured as D2/3 receptor binding potential (D2/3R-BP) in response to intragastric infusion of fat and glucose, between lean and obese subjects (before and after diet-induced weight loss). Correlations between gut-derived hormones and measured brain responses.

We hypothesize that:

1) Post-ingestion nutrient signals trigger striatal dopamine release, which may be disturbed (decreased) in obese individuals and thereby contribute to pathological feeding behavior.

2) Post-ingestion nutrient signals affect brain activity in brain regions involved in the regulation of food intake/feeding behavior and this effect will differ between lean and obese individuals: we expect obese individuals to show reduced post-ingestion nutrient signal-induced inhibition of brain activity in regions involved in homeostatic control of food intake, and reduced activation of brain areas involved in reward.

3) Diet-induced weight loss will change (increase) the dopaminergic response in the striatum to post-ingestion nutrient signals.

4) Diet-induced weight loss will improve the brain activity response to post-ingestion nutrient signals in obesity.

5) The effects of post-ingestion nutrient signals will depend on the type of macronutrient

Lean individuals:

- 1 Training session

- 3 fMRI sessions (water, glucose, lipid; random order)

- 2 SPECT sessions (one with glucose, one with intralipid; random order)



Obese individuals:

- Baseline: 1 training session, 3 fMRI sessions, 1 SPECT session (either with intralipid or glucose)

- During the diet: several visits to assess progress of weight loss

- Following the 3 month hypocaloric diet: 3 fMRI sessions, 1 SPECT session (intralipid or glucose)

Intra-gastric infusion of:

- 250 ml water

- 250 ml intralipid 20%

- 250 ml glucose 50%



Hypocaloric diet intervention: 3 months, aim to lose 10% of total bodyweight.