Lipid sensing along the oro-intestinal tract: impact on eating behavior and obesity risk – SENSOFAT2

Lipid sensing along the oro-intestinal tract: impact on eating behavior and obesity risk

Obesity reaches epidemic levels in the world. By reason of deleterious effects of obesity-associated diseases (i.e. type 2 diabetes, vascular disorders, hypertension, cancer), it is one of the major public health challenges of the 21rd century. During the past 20 years, its prevalence has tripled in many countries and the number of people affected continues to rise at an alarming rate, especially among children.
Chronic overconsumption of foods high in fat, coupled with a quantitative imbalance (i.e. excess saturated fat, cholesterol, high ratio omega6/omega3) has been identified as one of key factors of this epidemic. It was reported that laboratory rodents and humans display a spontaneous preference for fat through poorly known mechanisms. We have recently brought the first demonstration that a lipid-binding proteins (i.e. CD36) found both in the taste buds and gut, acts as a lipid-sensor implicated in the selection, digestion and absorption of fat-rich foods (ANR PRNA SensoFAT, 2008-2010). By promoting the efficiency of energy storage by the body, the original sensing system might constitute an evolutionary advantage to survive to periods of food scarcity. Conversely, it might be a risk factor for obesity in the case of continuous food abundance. Nevertheless, this lipid-sensing system is more complex than previously expected since G protein-coupled receptors (GPCR) might also play the role of lipid-sensors along the oro-intestinal tract. Moreover, lipid sensing in oral cavity and intestinal lumen seems to be hormone-sensitive. Finally, our growing knowledge about the pleiotropic actions of gut microbiota, which the diversity is modulated by dietary lipids, raises the question of its involvement in the regulation of oro-intestinal lipid sensing system.
The goal of the SensoFAT2 project is to further explore the mechanism of detection of dietary fat along the oro-intestinal axis by attempting to answer the following questions: What is (are) the respective role(s) of lipid-receptors found both in taste buds and small intestine? What are the cellular and molecular mechanisms involved? How are they regulated? Do nutritional, hormonal, microbiotal environment affect their function(s)?
Performed using various original mouse models, this investigation will be complementary to a clinical human trial (i.e. HumanFATaste program*) performed simultaneously in Dijon. Altogether data from these animal and human studies should lead to novel nutritional strategies and/or alternative pharmacological treatments in order to limit the consumption of foods high in fat and obesity risk.

(*) Funding (2010-2012): Centre National Inter-professionnel de l’Economie Laitière – CNIEL and Burgundy Council. Coordination: Pr P. Besnard U 866.