Increased liver oxidative stress and altered PUFA metabolism precede development of non-alcoholic steatohepatitis in SREBP-1a transgenic spontaneously hypertensive rats with genetic predisposition to hepatic steatosis.

The temporal relationship of hepatic steatosis and changes in liver oxidative stress and fatty acid (FA) composition to the development of non-alcoholic steatohepatitis (NASH) remain to be clearly defined. Recently, we developed an experimental model of hepatic steatosis and NASH, the transgenic spontaneously hypertensive rat (SHR) that overexpresses a dominant positive form of the human SREBP-1a isoform in the liver. These rats are genetically predisposed to hepatic steatosis at a young age that ultimately progresses to NASH in older animals.

Relationship between insulin resistance and muscle triglyceride content in nonobese and obese experimental models of insulin resistance syndrome.

In nonobese hereditary hypertriglyceridemic (HTg) rats and obese HTg Koletsky SHROB/Kol rats, muscle triglyceride accumulation and its relationship to glucose homeostasis and tissue sensitivity to insulin action were examined. Soleus muscle and diaphragm triglyceride contents were markedly increased in HTg rats as compared with controls and were further increased in obese animals. On the other hand, glucose intolerance and impairment of insulin-stimulated in vitro glycogen synthesis were of a similar degree in nonobese as well as obese animals.