|Rivera, Chantal - LOUISIANA STATE UNIV HSC|
|Abrams, Stephanie - BAYLOR COLLEGE OF MED|
|Tcharmtchi, Mohammad - BAYLOR COLLEGE OF MED|
|Allman, Monique - LOUISIANA STATE UNIV HSC|
|Ziba, Tina - BAYLOR COLLEGE OF MED|
|Finegold, Milton - BAYLOR COLLEGE OF MED|
|Smith, C Wayne|
Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 7, 2005
Publication Date: October 13, 2005
Citation: Rivera, C.A., Abrams, S.H., Tcharmtchi, M.H., Allman, M., Ziba, T.T., Finegold, M.J., Smith, C.W. 2005. Feeding a corn oil/sucrose-enriched diet enhances steatohepatitis in sedentary rats. American Journal of Physiology - Gastrointestinal and Liver Physiology. 290:G386-G393. Interpretive Summary: This paper demonstrates in a rat model that combining a high fat/high sucrose diet with a behavioral stress, hindlimb unloading (a model of sedentary behavior that promotes insulin resistance), increases liver inflammation and injury.
Technical Abstract: The current study investigated the combined effects of feeding a high-fat/high-sucrose (HF/HS) diet to rodents rendered sedentary via hindlimb unloading (HU). For 3 wk before HU, male Wistar rats were fed chow or a diet in which 32% of calories were derived from corn oil fat and 48% of calories from sucrose. Feeding continued during an additional 3-wk period of HU. Subsequently, blood samples were collected for determination of circulating leukocyte counts, insulin levels, and portal vein endotoxin. Inflammation, necrosis, and steatosis were assessed in formalin-fixed liver sections. No biochemical or histological evidence of injury was observed in control rats fed chow or HF/HS. HU increased circulating neutrophils and resulted in hyperinsulinemia. Mild hepatic fat accumulation and minimal focal necroinflammation were observed in this group. Feeding HF/HS during HU exacerbated hyperinsulinemia, hepatic steatosis, Kupffer cell content, and cytokine expression. Significant portal endotoxemia was noted in HU rats but was not influenced by HF/HS diet. On the other hand, feeding HF/HS significantly enhanced lipid peroxidation end products in liver of HU rats by approximately threefold compared with chow-fed rats. In summary, these findings demonstrate that feeding a high-calorie diet potentiates steatosis and injury in sedentary HU rats. Mechanisms underlying enhanced injury most likely involved lipid peroxidation. Importantly, these findings suggest that dietary manipulation combined with physical inactivity can be used to model steatohepatitis.