Sugar and Fat Absorption Increased In Obesity

Dr. Karine Clément M.D., Ph.D. Assistant Professor, Nutrition Department Hotel-Dieu hospital ParisMedicalResearch.com Interview with:
Prof. Karine Clément MD, PhD

Director ICAN – Institute of Cardiometabolism And Nutrition
Hôpital La Pitié-Salpêtrière, Paris
www.ican.paris
k.clement@ican-institute.org

Medical Research: What is the background for this study? What are the main findings?

Dr. Clément: Obesity, associated with insulin resistance, is a chronic inflammatory disease revealed by a moderate but long-term increase in the levels of inflammatory molecules in the blood.

Our groups and others have shown that several organs such as adipose tissues, liver, pancreas and muscles are also sites of inflammation with accumulation of immune cells such as macrophages and lymphocytes. This low-grade inflammatory state perturbs the tissue biology and contributes to the development and/or maintenance of insulin resistance and diabetes. In addition our teams and others showed that the intestinal functions are altered in obesity such as sugar and lipid absorption of and enteroendocrine nutrient signaling to the whole body.

Our teams showed modifications of immunity in the obese intestine, and particularly in the jejunum part where most of sugar and lipid absorption takes place. Obesity increases the absorptive surface of the intestine and the colonization of the epithelium by CD8αβ T lymphocytes not affecting tissue integrity, thus differing from IBD inflammation. The cytokines secreted by the CD8 T cells of obese, but not lean subjects, are able to inhibit insulin action in enterocytes. In these patients, the increase of intestinal CD8 T cell density correlates with sugar absorption capacity and with the level of obesity and associated complications such as liver disease (NASH – Non-Alcoholic SteatoHepatitis) and dyslipidemia.

Medical Research: What should clinicians and patients take away from your report?

Dr. Clément: There has been tremendous progress in understanding the complex pathophysiology of obesity and, particularly through the identification of the pathological alteration of organs starting with the alteration of the adipose tissues during obesity development.

Obesity is not only simply driven by excessive eating and insufficient physical activity, it is evidently a complex disease relying on pathological crosstalk between many organs (brain, adipose tissue, muscle, liver pancreas) with functional alteration.

Thanks to the extensive clinical phenotyping of obese subjects in our study, it is possible to include the small intestine as a contributor in this complex crosstalk. In particular, sugar and fat absorption is increased in an insulin resistant body and therefore in obesity. Furthermore, the intestinal mucosa is a physical and immune barrier sensing bacterial and food antigens. Here we show that changes in intestinal immunity and inflammation might contribute to metabolic perturbation in obese subjects.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Clément: Next aims are to understand how deeply these perturbations of the intestine impact on the human body; in particular, how the gut microbiota, the intestinal immune system and beyond the gut, body metabolism are interrelated. Gut microbiota is indeed perturbed in obesity and diabetes. Non-invasive intervention targeting intestinal inflammation in relation to nutrient and local microbiota could help gain metabolic health

Citation:

Milena Monteiro-Sepulveda, Sothea Touch, Carla Mendes-Sá, Sébastien André, Christine Poitou, Omran Allatif, Aurélie Cotillard, Hélène Fohrer-Ting, Edwige-Ludiwyne Hubert, Romain Remark, Laurent Genser, Joan Tordjman, Kevin Garbin, Céline Osinski, Catherine Sautès-Fridman, Armelle Leturque, Karine Clément, Edith Brot-Laroche. Jejunal T Cell Inflammation in Human Obesity Correlates with Decreased Enterocyte Insulin Signaling. Cell Metabolism, 2015; DOI: 10.1016/j.cmet.2015.05.020