Skip to main content

Nutrient Sensing In Satiety Control and Obesity

Final Activity Report Summary - NUSISCO (Nutrient sensing in satiety control and obesity)

The 'Nutrient Sensing In Satiety Control and Obesity' (NUSISCO) project was a programme on all aspects of feeding behaviour and control of food intake and appetite through the collaboration between three European Universities and a major European / global food company involved in the control of appetite, i.e. molecules and cells, integrative physiology, clinical science/behaviour, nutritional and food science. The aim was to give the students a concrete view of the complexity of appetite control. To conduct the research programme, each PhD student has been assigned to a research project contributing to the research objectives under a co-ordinated partnership between the 4 partners. NUSISCO has delivered key insights in:

1- Intestinal endocrine cell models for luminal nutrient sensing (mainly leaded by TUM)
The main objectives were to develop an in vitro or ex vivo screening system for gut sensory active ligands. Using these screening techniques, several compounds were found to trigger gut hormone secretion. We identified the intestinal peptide transporter PEPT1, and the bitter receptor TAS2R14 as sensors. As for PEPT1, a novel signal transduction pathway involving cellular cross-talk between enterocytes and endocrine cells was identified. Interestingly, different diets induce obesity in the mouse, but the metabolic consequences are different. In general, obese mice had a higher liver fat content and altered gut flora. Important changes in gene expression in liver and intestine in animals receiving a high fat diet compared to a cafeteria diet were observed. The texture of the food is important in diet induced obesity since diet supplied in powder form and not as standard pellets lead to an obese phenotype.

2- Nutrient-induced satiety signal to the brain (mainly lead by agroparistech)
This project aimed to better understand the mechanisms by which nutrient induce satiety. Concerning fat we found that
(i) an increment in fat and energy intake triggers decreased brain-derived neurotrophic factor anorexigenic signalling; and
(ii) a high-fat diet leads to desensitisation to the anorexigenic peptide cholecystokinin.
Concerning protein induced satiety we showed that vagal capsaicin sensitive fibres are not necessary for high protein diet induced hypophagia. Secondly comparing brain 3D activity in response to nutrient loads, activations were found on distinct positions in the NTS. Finally, we showed that the effect of HP intake causing lower adiposity resulted from reduced postprandial lipogenesis.

3- Human clinical experimentation on the influence of nutrients on gut hormones and food intake (mainly leaded by Imperial College)
The main purpose of the project was to explore the link between food, the gut and the central nervous system in humans. we have demonstrated that
(i) high intakes of fermentable carbohydrate release appetite regulating gut hormones leading to a suppression of appetite;
(ii) artificial sweeteners have no effect on appetite regulation;
(iii) stress had no effect on appetite regulation
(iv) Gut hormones work in synergy;
(v) an infusion of oxyntomodulin and PYY have greater appetite suppression than either peptide on its own;
(vi) finally we have demonstrated that fasting biases brain reward systems towards high-calorie foods.

4- Design of in vitro / in vivo non-invasive models for nutrient signalling (mainly leaded by Unilever
The objective of this project was primarily to identify 'sensors' that responsible for the recognition of substrates/nutrients and signal transduction into the cell based on the so-called bitter and sweet taste receptors. By measuring calcium release and release of hormones and using 'libraries' of different sweet and bitter compounds, some compounds triggering these sensors were identified. Furthermore, some molecular targets involved in dietary peptide sensing by specialised GI cells were identified as well.