In metabolic disorders such as diabetes mellitus or obesity, a modification of the fecal flora, an increase of the bacterial translocation, or a decrease in the integrity of the intestinal barrier, is observed. The worldwide obesity epidemic contributes to the increasing incidence of a number of diseases, as Non-Alcoholic Fatty-Liver Disease (NAFLD) and its most severe form, the Non-Alcoholic-Steato-Hepatitis (NASH).

Probiotic treatment reduces blood glucose levels in diabetic rats

Data on the prevalence of NASH has varied from 18.5% (5) to 69% (43) in obesity (de Oliveira, Ann Hepatol, 2007). Recently, it has been demonstrated that probiotic treatment reduces blood glucose levels in diabetic rats (Al-Salami, 2008) and improves high-fat-diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells.

Characterizing properties

We are able to characterize adipogenic properties of ligands or nutriments in vitro and in vivo, and to evaluate the integrity of the intestinal barrier and the modification of the fecal flora or bacterial translocation in the model of obese and/or diabetic mice.

Evaluating in vitro effects

We can evaluate the in vitro effects of ligands or nutriments on adipocyte differentiation using 3T3-L1 cells and specific coloration or quantification of specific gene expression. In vivo, several animal models are available: genetically modified animal model (ob/ob, db/db); obese and diabetic mice induced by high-fat diet associated tools; conventional bacteriologic analysis of the flora and the bacterial translocation; evaluation of intestinal barrier integrity (FITC-dextran, lactulose/mannitol test, expression of specific gene by real-time PCR, IHC or WB); dosage of lipidemia, glycemia by conventional biochemical analysis; and a test of insulin resistance.


Regulation of the cell cycle and the apoptosis techniques used Real Time PCR, ELISA, Western Blot, Immunocytochemistry. In vivo studies inflammation: hepatitis induced by chemical agent. The acute carbon tetrachloride (CCl4) intoxication is the widely used model of hepatitis. It is able to induce acute inflammation. Concanavaline (ConA) is able to induce a rapid and reliable hepatitis mediated by lymphocytes.

Similarities with the human autoimmune hepatitis

This model shares some similarities with the human autoimmune hepatitis. In bile-induced hepatitis, ligation of the extrahepatic bile duct leads to an acute hepatitis. Inflammation is evaluated using histology, plasma level of transaminases, and liver expression of mediators of inflammation (cytokines). Fibrosis chronic exposition to CCl4 leads to an important liver fibrosis. Fibrosis is graded using specific staining of liver histological specimens (sirus red, METAVIR scoring), hydroxyproline content, quantification of fibrogenic mediators (SMA, collagen, TGF).

Liver regeneration

Liver regeneration: The two-thirds partial hepatectomy in mice is a reliable model to study the effects of compounds on liver regeneration. Hepatocyte regeneration could also be evaluated after acute CCl4 intoxication. In both models, liver regeneration is evaluated using macroscopic (liver weight gain) and histological (mitotic index and BrdU index) parameters. Liver levels of protein involved in acute phase (TNF, IL-6) and cell cycle (cyclin D1, c-myc) are quantified.

Which model to choose?

Based on our expertise, we will propose the most relevant animal model to evaluate the therapeutic properties of tested compounds.