Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH.
OBJECTIVE
Replacing long-chain triacylglycerols (LCT) with medium-chain triacylglycerols (MCT) reduces alcohol-induced liver injury. Because of the similarity of the pathogenesis of alcohol-induced liver damage and non-alcoholic steatohepatitis (NASH), our aim was to assess whether MCT is also beneficial in NASH.


METHODS
We used a rat NASH model in which corn oil (35% of total calories) was isocalorically replaced with MCT.


RESULTS
Partial replacement of LCT did not ameliorate hepatic fat accumulation, 4-hydroxynonenal, collagen type I and its mRNA but it increased TNF-alpha and its mRNA (p<0.001). However, in rats given the high-fat diet restricted to 2/3 of the amount they were consuming, these adverse effects decreased, with and without MCT including less liver steatosis and lower triacylglycerols, but without beneficial effects of MCT. When 70% of the fat calories were replaced with MCT with no LCT remaining in the diet, no steatosis developed and hepatic TNF-alpha was low. When all MCT were given with carbohydrates (instead of LCT) hepatic TNF-alpha also decreased (p<0.001).


CONCLUSIONS
MCT are not hepatotoxic, provided the diet contains no significant amount of LCT. Total replacement of dietary LCT with MCT fed ad libitum is beneficial whereas partial replacement becomes hepatotoxic, unless the dietary intake is restricted.
Lieber
Charles S
CS
Alcohol Research Center, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468, USA. liebercs@aol.com
DeCarli
Leonore M
LM
Leo
Maria A
MA
Mak
Ki M
KM
Ponomarenko
Anatoly
A
Ren
Chaoling
C
Wang
Xiaolei
X
D000818:Animals; D049109:Cell Proliferation; D024042:Collagen Type I / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D004041:Dietary Fats / Q000008:administration & dosage; D005234:Fatty Liver / Q000188:drug therapy*; D022781:Hepatocytes / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D024042:Collagen Type I; D004041:Dietary Fats; D011347:Procollagen; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D019392:Cytochrome P-450 CYP2E1