|RONIS, MARTIN - University Arkansas For Medical Sciences (UAMS)|
|MERCER, KELLY - University Arkansas For Medical Sciences (UAMS)|
|SUVA, LARRY - University Arkansas For Medical Sciences (UAMS)|
|BADEAUX, JAMIE - Arkansas Children'S Nutrition Research Center (ACNC)|
|FERGUSON, MATTHEW - University Arkansas For Medical Sciences (UAMS)|
|HOGUE, WILLIAM - University Arkansas For Medical Sciences (UAMS)|
|SHARMA, NEHA - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: Toxicologist
Publication Type: Abstract Only
Publication Acceptance Date: 11/1/2011
Publication Date: 3/15/2012
Publication URL: http://www.toxicology.org/AI/PUB/Toxicologist12.pdf
Citation: Ronis, M.J., Mercer, K., Suva, L., Badeaux, J., Ferguson, M., Hogue, W., Sharma, N., Badger, T.M. 2012. Effect of dietary fat/carbohydrate ratio on progression of alcoholic liver injury and bone loss in rats fed via total enteral nutrition (TEN). The Toxicologist. 126(S1):76 - Abstract#PS-356.
Technical Abstract: Few studies have examined the effects of diet on the dynamics of injury progression or on alcohol-induced bone loss. In the current study, 300 g male Sprague-Dawley rats (N = 10/group) were treated with alcohol containing liquid diets via a stomach tube. Dietary fat content was either 5% (high carbohydrate, HC) or 45% (high fat), with or without ethanol (EtOH) substitution for carbohydrate calories to a final level of 13 g/kg/d. After treatment for 14, 28 or 67 d, rats were sacrificed and liver and tibial bone analyzed. HC rats gained more weight and had larger fat pads than HF rats with or without EtOH, but blood EtOH values did not differ. Liver fat content increased more rapidly in EtOH/HC rats than EtOH/HF rats accompanied by increases in mRNAs encoding genes involved in fatty acid (FA) synthesis. However, over time, control rats also developed fatty livers associated with increased expression of the FA transporter CD36. Genes related to FA degradation were elevated by EtOH independent of diet but no effects were observed on genes associated with lipoprotein synthesis and fat export to other tissues. Despite higher levels of liver fat, HC/EtOH rats had no increase in oxidative stress until d67 and no increases in liver cell death relative to controls. In contrast HF/EtOH rats had increased oxidative stress from d 28 and increased liver injury over controls and higher expression of two liver enzymes (CYP2E1 and CYP4A1) known to produce oxygen radical over HC/EtOH rats by d 67. In contrast, no dietary differences were observed on EtOH-induced loss of bone mineral density or strength. These data demonstrate that diet composition is an important factor in development of alcoholic liver injury but that this does not extend to other organs damaged by alcohol such as bone.