Author:
Baumgardner January N.,Shankar Kartik,Hennings Leah,Badger Thomas M.,Ronis Martin J. J.
Abstract
We have used total enteral nutrition (TEN) to moderately overfeed rats high-polyunsaturated fat diets to develop a model for nonalcoholic steatohepatitis (NASH). Male Sprague-Dawley rats were fed by TEN a 187 kcal·kg−3/4·day−1 diet containing 5% (total calories) corn oil or a 220 kcal·kg−3/4·day−1 diet in which corn oil constituted 5, 10, 25, 35, 40, or 70% of total calories for 21 or 65 days. Rats fed the 5% corn oil, 220 kcal·kg−3/4·day−1 diet had greater body weight gain ( P ≤ 0.05), fat mass ( P ≤ 0.05), and serum leptin and glucose levels ( P ≤ 0.05), but no liver pathology. A dose-dependent increase in hepatic triglyceride deposition occurred with increase in percent corn oil in the 220 kcal·kg−3/4·day−1 groups ( P ≤ 0.05). Steatosis, macrophage infiltration, apoptosis, and focal necrosis were present in the 70% corn oil group, accompanied by elevated serum alanine aminotransferase (ALT) levels ( P ≤ 0.05). An increase in oxidative stress (thiobarbituric acid-reactive substances) and TNF-α expression ( P ≤ 0.05) was observed in the 70% corn oil group, as well as an increase in hepatic CYP2E1 and CYP4A1 expression ( P ≤ 0.05). Significant positive correlations were observed between the level of dietary corn oil and the degree of pathology, ALTs, oxidative stress, and inflammation. Liver pathology was progressive with increased necrosis, accompanied by fibrosis, observed after 65 days of TEN. Increased expression of CD36 and l-fabp mRNA suggested development of steatosis was associated with increased fatty acid transport. These data suggest that intragastric infusion of a high-polyunsaturated fat diet at a caloric level of 17% excess total calories results in pathology similar to clinical NASH.
Publisher
American Physiological Society
Subject
Physiology (medical),Gastroenterology,Hepatology,Physiology
Reference88 articles.
1. Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis
2. Badger TM, Crouch J, Irby D, Hakkak R, Shahare M. Episodic excretion of ethanol during chronic intragastric ethanol infusion in the male rat: continuous vs. cyclic ethanol and nutrient infusions. J Pharmacol Exp Ther 264: 938–943, 1993.
3. Pulsatile blood alcohol and CYP2E1 induction during chronic alcohol infusions in rats
4. Badger TM, Ronis MJ, Lumpkin CK, Valentine CR, Shahare M, Irby D, Huang J, Mercado C, Thomas P, Ingelman-Sundberg M, Crouch J. Effects of chronic ethanol on growth hormone secretion and hepatic cytochrome P450 isozymes of the rat. J Pharmacol Exp Ther 264: 438–447, 1993.
5. Undernutrition enhances alcohol-induced hepatocyte proliferation in the liver of rats fed via total enteral nutrition
Cited by
103 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献