Skip to Main content Skip to Navigation
Theses

Stéatohépatite et adaptations métaboliques:
Effets d'un régime enrichi en lipides saturés, ou carencé en choline et méthionine, sur la bioénergétique et le métabolisme hépatique de rat

Abstract : Non alcoholic steatohepatitis (NASH) is a raising pathology in northern countries, due to obesity and insulin-resistance. To date, NASH pathogenesis is poorly understood because suitable animal models are missing and an appropriate treatment to prevent patient NASH evolution in cirrhosis is still lacking. The aim of this work was to study the bioenergetic and metabolic modifications in hepatocyte and liver mitochondria isolated from NASH suffering rats.
In a first part, we elaborated a diet with saturated fatty acids to induce a NASH. After 14 weeks of both diets, no steatosis could be observed in the rat livers. Studies carried out on isolated hepatocytes and liver mitochondria showed no modification in the liver bioenergetic or metabolism characteristics in comparison to control rats. By contrast, a modification in tissue repartition was observed, with a mass increase in white and brown adipose tissues. In this study, the absence of liver steatosis might be due to a huge increase in white adipose tissue storage and thermogenic lipid oxidation in the brown adipose tissue, to “burn” the caloric excess.
The second part of this work was devoted to study bioenergetic and metabolic modifications induced by a choline and methionine deficient diet, known to induce NASH in rats. Liver mitochondria and hepatocytes isolated from treated rats presented an increase in the respiration rate. This higher oxygen consumption was due to an uncoupling of the respiratory chain by a “proton leak” and a “redox slipping” at the cytochrome c oxidase level. This uncoupling yielded in higher lipid oxidation and lower reactive oxygen species production. Moreover, studies with isolated hepatocytes showed an increased lipid oxidation and neoglucogenesis.
These results suggest mitochondrial and metabolic adaptations of NASH rat liver which permit to limit a lipid overload and an oxidative stress
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-00262387
Contributor : Frédérique Cohen-Adad <>
Submitted on : Tuesday, March 11, 2008 - 3:54:52 PM
Last modification on : Wednesday, November 20, 2019 - 2:41:01 AM
Long-term archiving on: : Thursday, May 20, 2010 - 9:51:12 PM

Identifiers

  • HAL Id : tel-00262387, version 1

Collections

Citation

Caroline Romestaing. Stéatohépatite et adaptations métaboliques:
Effets d'un régime enrichi en lipides saturés, ou carencé en choline et méthionine, sur la bioénergétique et le métabolisme hépatique de rat. Physiologie [q-bio.TO]. Université Claude Bernard - Lyon I, 2007. Français. ⟨tel-00262387⟩

Share

Metrics

Record views

556

Files downloads

4306