Title of project

Hormonal control of energy and mactronutrient intake in obesity: The MEMORY study

Abstract

Background: Obesity is associated with higher preference for foods high in fat and sugar, but the reason for this is unknown. Glucagon and gastrointestinal hormones, e.g., glucagon-like peptite-1, ghrelin, and peptide YY play a crucial role in appetite con-trol and satiety and seem to be involved in food reward and food preferences. Fur-thermore, the liver is a key organ in the metabolic control of appetite and is likely to play a role in obesity development. One of the hormones secreted from the liver, Fi-broblast Growth Factor 21 (FGF21), is increased in response to intake of high carbohy-drate diets and to lack of dietary protein. There is a need for well-controlled human studies investigating whether food preferences and components of food reward are affected by different macronutrients, how they are related to metabolic markers of appetite, and in which way they change in obesity and during weight loss. Likewise, human studies examining the role of macronutrient manipulation on plasma FGF21 and glucagon levels as well as subsequent food intake are lacking.

Objective: To examine the concept of ‘food memory’ – in other words whether the macronutrient composition of the diet influences subsequent sensory-specific prefer-ence and macronutrient intake as well as the hormonal response – and whether these are affected by obesity and recent weight loss. Furthermore, to identify unexplored circulating metabolites and proteins associated with macronutrient intake and senso-ry-specific food memory using metabolomics and proteomics.

Methods: 45 men and women will be included in a randomized cross-over study: 15 with normal weight (BMI<25 kg/m2), 15 with obesity (BMI≥30 kg/m2), and 15 who have obtained a ≥5% weight loss within 8 weeks. Each participant will undergo the same visit two times (but with different macronutrient composition of the test meal). The following isocaloric test meals will be served: 1) high carbohydrate/low protein, and 2) high protein/low carbohydrate. Subjective appetite, food preferences, metabolites and appetite-related hormones will be assessed in the fasted state and repeatedly for 4 hours after the meals. Food preferences will be assessed using the Steno Biometric Food Preference Task, which has been developed by the research group and collabo-rators. Unexplored circulating metabolites and proteins will be measured using omics technology at Novo Nordisk A/S.

Impact: Results from this project has the potential to change our understanding of obesity and can be used to target prevention strategies for obesity and type 2 diabetes in the future.