Microenvironnement intestinal et résistance à l'insuline des entérocytes dans le développement des dyslipidémies athérogènes

 

Alain Veilleux

Institut sur la nutrition et les aliments fonctionnels (INAF)

 

Domaine : Nutrition et métabolisme

Programme chercheurs-boursiers - Junior 1

Concours 2016-2017

Recent studies have demonstrated that the small intestine plays a key role in the development of postprandial dyslipidemia in insulin-resistant and type 2 diabetic patients. Alterations have been observed in several important functions of enterocytes, the absorptive cells of the intestine. Presence of an insulin-resistant state in the enterocytes has been suggested as a possible mechanism promoting gut dysfunctions in presence of obesity. Given that the small intestine is a key interface between the environment and the host, enterocytes are potentially exposed to several bioactive factors from the intestinal microenvironment. We hypothesized that alterations in the intestinal microenvironment lead to the development of an insulin-resistant state in the intestine and consequently contribute to enterocyte dysfunction.

The objective of this research program is to elucidate intestinal microenvironment factors and mechanisms involved in enterocyte dysfunction and contributing to the development of postprandial dyslipidemia. An innovative and highly relevant culture model of human enterocytes will be used to assess the impact of several obesity-related factors on insulin sensitivity and functions of enterocytes. Both factors from the environment (nutrients and bacteria) and the host (nutrients, hormones and inflammation) will be considered in the study. In addition, impact of these factors as well as mechanisms involved will be confirmed in an animal model of diet-induced obesity.

The proposed research program will contribute to the elucidation of mechanisms promoting postprandial atherogenic dyslipidemia, which is associated with an elevated cardiovascular disease risk. This research program is part of an overall goal to identify potential strategies for pharmacological and nutritional treatments of the dyslipidemia associated with insulin resistance through an eventual modulation of the intestinal microenvironment.