TY - JOUR
T1 - Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH
AU - Lieber, Charles S.
AU - DeCarli, Leonore M.
AU - Leo, Maria A.
AU - Mak, Ki M.
AU - Ponomarenko, Anatoly
AU - Ren, Chaoling
AU - Wang, Xiaolei
N1 - Funding Information:
This study was supported by the Office of Research and Development, Department of Veterans Affairs, NIH Grant AT001583 and the Kingsbridge Research Foundation.
PY - 2008/2
Y1 - 2008/2
N2 - Background/Aims: 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-α 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-α was low. When all MCT were given with carbohydrates (instead of LCT) hepatic TNF-α 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.
AB - Background/Aims: 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-α 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-α was low. When all MCT were given with carbohydrates (instead of LCT) hepatic TNF-α 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.
KW - Long-chain triacylglycerols
KW - Medium-chain triacylglycerols
KW - Non-alcoholic steatohepatitis
KW - TNF-α
UR - https://www.scopus.com/pages/publications/37849028988
U2 - 10.1016/j.jhep.2007.09.016
DO - 10.1016/j.jhep.2007.09.016
M3 - Article
C2 - 18093684
AN - SCOPUS:37849028988
SN - 0168-8278
VL - 48
SP - 318
EP - 326
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 2
ER -