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Hepatocyte growth factor leads to recovery from alcohol-induced fatty liver in rats
Minoru Tahara, … , Toshihiro Nukiwa, Toshikazu Nakamura
Minoru Tahara, … , Toshihiro Nukiwa, Toshikazu Nakamura
Published February 1, 1999
Citation Information: J Clin Invest. 1999;103(3):313-320. https://doi.org/10.1172/JCI4433.
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Article

Hepatocyte growth factor leads to recovery from alcohol-induced fatty liver in rats

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Abstract

A fatty liver is characterized by the hyperaccumulation of lipids within hepatocytes and is often caused by excessive alcohol intake. Rats fed ethanol-containing diets for 37 days showed remarkable increase in hepatic lipids and lipid droplet accumulation in the hepatocytes, indicating the onset of alcoholic fatty liver. Administration of hepatocyte growth factor (HGF) for the last seven days of ethanol treatment markedly decreased hepatic lipids to a level lower than that seen before HGF treatment. In contrast, serum levels of lipids and lipoproteins increased with HGF administration. Primary cultured hepatocytes prepared from the fatty liver retained lipid droplets during a 48-hour culture. However, when cultured in the presence of HGF, intracellular lipid concentrations decreased and lipid secretion was enhanced. Consistent with these events, HGF stimulated the rate of protein synthesis of apolipoprotein B (apoB) and enhanced subsequent mobilization of lipids into the medium. These results indicate that HGF administration induced recovery from the fatty liver, at least in part, by enhancing apoB synthesis and the subsequent mobilization of lipids from hepatocytes with fatty change. The possibility that HGF can be therapeutic for subjects with an alcohol-related fatty liver warrants further attention.

Authors

Minoru Tahara, Kunio Matsumoto, Toshihiro Nukiwa, Toshikazu Nakamura

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Figure 1

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HGF-induced changes in hepatic lipid contents in rats with alcoholic fat...
HGF-induced changes in hepatic lipid contents in rats with alcoholic fatty liver. Rats were pair-fed isocaloric liquid diets for 30 days (n = 4), or ethanol-containing diets for 30 days (n = 4) or 37 days. hrHGF (n = 6) or saline (n = 6) alone was daily injected for the last 7 days during a 37-day treatment with ethanol diets. Each value represents the mean ± SD. #P < 0.05, ##P < 0.01 ethanol-fed rats vs. pair-fed rats; *P < 0.05, **P < 0.01 HGF-treated rats vs. saline control. HGF, hepatocyte growth factor; hrHGF, human recombinant hepatocyte growth factor.

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