|Ronis, Martin -|
|Baumgardner, January -|
|Sharma, Neha -|
|Badeaux, Jamie -|
|Ferguson, Matthew -|
|Tong, Yudong -|
|Wu, Xianli -|
|Cleves, Mario -|
Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 21, 2012
Publication Date: February 15, 2013
Citation: Ronis, M.J., Baumgardner, J.N., Sharma, N., Badeaux, J., Ferguson, M.E., Tong, Y., Wu, X., Cleves, M.A., Badger, T.M. 2013. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease. Experimental Biology and Medicine. 238(2):151-162. Interpretive Summary: Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome"(MS), often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and resulting in the need for a transplant. Replacing corn oil with medium chain fats (MCT) in the diets of alcohol-fed rats has been shown to protect against development of fatty liver and alcoholic liver injury. The current study was designed to determine if a similar effect occurs in a rat model with non-alcoholic fatty liver disease. Groups of male rats were overfed diets containing increasing proportions of corn oil or a high fat diet in which corn oil was replaced with increasing concentrations of saturated fat. As dietary content of corn oil increased, liver fat and markers of liver damage were increased. This was accompanied by higher levels of proteins that generate damaging products and higher levels of polyunsaturated fatty acids (FA) in the liver. Increasing the proportion of MCT-enriched saturated fat resulted in a dose-dependent reduction in liver fat and liver damage. Increasing the ratio of MCT to corn oil: reduced liver polyunsaturated fatty acid concentrations, reduced membrane susceptibility to injury, and stimulated fatty acid breakdown. These data suggest that replacing unsaturated fats like corn oil with MCT oil in the diet could be utilized as a potential treatment for non-alcoholoc fatty liver disease.
Technical Abstract: Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been shown to protect against steatosis and alcoholic liver injury. The current study was designed to determine if a similar beneficial effect of MCT occurs in a rat model of NAFLD. Groups of male rats were isocalorically overfed diets containing 10%, 35%, or 70% total energy as corn oil or a 70% fat diet in which corn oil was replaced with increasing concentrations of saturated fat (18:82, beef tallow:MCT oil) from 20% to 65% for 21 d using total enteral nutrition (TEN). As dietary content of corn oil increased, hepatic steatosis and serum ALTs were elevated (P<0.05). This was accompanied by greater expression of cytochrome P450 enzyme CYP2E1 (P<0.05) and higher concentrations of polyunsaturated 18:2 and 20:4 fatty acids (FA) in the hepatic lipid fractions (P<0.05). Keeping the total dietary fat at 70%, but increasing the proportion of MCT-enriched saturated fat, resulted in a dose-dependent reduction in steatosis and necrosis without affecting CYP2E1 induction. There was no incorporation of C8-C10 FAs into liver lipids, but increasing the ratio of MCT to corn oil: reduced liver lipid 18:2 and 20:4 concentrations; reduced membrane susceptibility to radical attack; stimulated FA beta- and '-oxidation as a result of activation of peroxisomal proliferator activated receptor (PPAR)alpha, and appeared to increase mitochondrial respiration through complex III. These data suggest that replacing unsaturated fats like corn oil with MCT oil in the diet could be utilized as a potential treatment for NAFLD.