Study Title:

Gut Bacteria's Toxic Trigger for Metabolic Problems

Study Abstract

Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat-fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.

Study Information

Patrice D. Cani; Jacques Amar; Miguel Angel Iglesias; Marjorie Poggi; Claude Knauf; Delphine Bastelica; Audrey M. Neyrinck; Francesca Fava; Kieran M. Tuohy; Chantal Chabo; Aurélie Waget; Evelyne Delmée; Béatrice Cousin; Thierry Sulpice, et al.
Metabolic Endotoxemia Initiates Obesity and Insulin Resistance
Diabetes
2007 August
Institute of Molecular Medicine, I2MR Toulouse, France.

Full Study

http://www.medscape.com/viewarticle/560887