Grant: Operating Grant

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 enterocytes has been suggested as a possible mechanism promoting enterocyte dysfunction 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 promote enterocyte dysfunction. The objective of this research project is to elucidate intestinal microenvironment factors and mechanisms involved in enterocyte dysfunction and 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 enterocyte functions. Factors from the environment (nutrients and bacteria) and from the host (nutrients, hormones and inflammation) will be considered in this project. In addition, mechanisms involved in gut dysfunction will be confirmed in an animal model of diet-induced obesity. The proposed research project will contribute to the elucidation of mechanisms promoting postprandial atherogenic dyslipidemia, which is associated with an elevated cardiovascular disease risk. This project is part of an overall goal to identify potential strategies for pharmacological and nutritional treatments of postprandial dyslipidemia associated with insulin resistance.