Ameliorating Fatty Liver through Oral Administration of Docosahexaenoic Acid and Lysine in Mice
Date Issued
2011
Date
2011
Author(s)
Lin, Hsin-Yu
Abstract
Fatty liver disease (FLD) is a worldwide illness, characterized with significant amount of triglyceride accumulation in the liver cells. Fatty liver progression with inflammation, FLD may further develop into fibrosis, cirrhosis and liver failure, or toward hepatocellular carcinoma. Docosahexaenoic acid (DHA) is one of essential n-3 polyunsaturated fatty acids for human. Treatment of DHA has been shown to decrease the expression of lipogenic genes and prevent some illnesses, such as cardiovascular diseases. In addition to its critical role to animal growth, lysine plays a fundamental role in carnitine synthesis, a nutrient that helps to convert fatty acids into energy. It has been shown that lysine treatment protects rats against hepatotoxic actions of D-galactosamine. Therefore, this study was designed to investigate the effects of DHA and lysine on non-alcoholic FLD.
In the in vivo study, 48 C57B/6 mice were fed with high fat diet containing 35.5% fat for 23 weeks. They were then divided into 6 groups, with oral administration of saline, 0.5% (based on daily dietary intake) lysine, 1% lysine, 1% DHA, 1% DHA + 0.5% lysine and 1% DHA + 1 % lysine for 4 weeks. Mice with high fat diet exhibited heavier body weight than those fed with control chow diet. Histological examination showed that significant and numerous fat droplets accumulated in the liver of mice with high fat diet. Compared with the saline group, mice administrated with DHA or lysine or combined with both at any given levels exhibited a decrease of body weight. Furthermore, serum triglyceride levels and alanine transaminase activities were remarkably reduced in the groups fed with DHA, indicating that DHA may reduce fat accumulation to protect liver from steatosis. Indeed, the suggestion was supported by a decrease of the transcript levels of proinflammatory cytokines genes such as tumor necrosis factor-α, interleukin 1β and monocyte chemotactic protein-1 and lipogenic gene expreesions, such as fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1) in the liver of mice with DHA treatment. Both the treatments of DHA and lysine decreased the accumulation of hepatic lipid droplets. Additionally, reduced mRNA expressions of FAS and ACC1 in mice gonadal adipose tissues by DHA treatment were observed.
In the in vitro studies, human hepatocellular carcinoma SK-HEP-1 cells were treated with 1 mM oleic acid in order to establish a cell model for fatty liver. After 24 hr culture, the steatotic hepatocytes were treated with 0.1 mM DHA, 4 mM lysine respectively or with 0.1 mM DHA + 4 mM lysine for 24 hr in the presence of or without OA. Results showed that the treatments significantly downregulated FAS and interleukin 6 transcription levels by DHA and lysine.
In conclusion, the present study suggests that DHA treatment decreases mice serum TG levels and ALT activities and reduced the hepatic lipid droplet accumulation. Moreover, treatment of DHA decreases lipogenic and inflammatory gene expressions and contributes to the amelioration of fatty liver. Lysine exerted effects only on decreasing lipid accumulation in the liver, and its regulatory mechanism required further studies. Based on the results above, foods abundant with DHA or lysine may have a high therapeutic potential in the amelioration of non-alcoholic fatty liver disease.
Subjects
fatty liver
DHA
lysine
mice
SDGs
Type
thesis
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