Abstract

BackgroundLipid metabolism is altered in subjects with liver steatosis. FAS is a key enzyme in de novo lipogenesis and both FAS gene expression and enzymatic activity are primarily regulated by metabolic signals in the liver. Lipoprotein lipase (LPL), the rate-limiting enzyme for the hydrolysis of core triglycerides, plays a pivotal role in lipid metabolism. This study aims to investigate if circulating levels of FAS and LPL could be clinically associated with liver steatosis.MethodsIn this work, we present data obtained from a subsample of 94 subjects with liver steatosis enrolled by NUTRIEPA study, a nutritional trial in subjects with liver steatosis. Serum levels of FAS protein and LPL activity were evaluated by ELISA test and by a fluorescent method, respectively. The diagnosis and the degree of liver steatosis were based on laboratory and ecographic measurements. Statistical methods included Kruskal-Wallis analysis of variance and Wilcoxon signed-rank test, where appropriate. The χ2 test has been performed to analyse categorical variables.ResultsThe subjects with severe steatosis had significantly higher serum levels of FAS protein and LPL activity compared to subjects with mild and moderate liver steatosis. Moreover, a positive trend in serum levels of FAS expression from lower to higher degree of steatosis was also detected.ConclusionsWe describe a relationship between human liver steatosis and elevated levels of circulating lipogenic enzymes. Increased serum levels of FAS expression and LPL activity could be considered a marker of severe liver steatosis.

Highlights

  • Liver steatosis may be considered the consequence of an increased influx of free fatty acids or a decreased export of lipids through very low density lipoprotein (VLDL), less fatty acid oxidation or increased de novo lipogenesis in the liver [1]

  • Liver steatosis is frequent in patients with metabolic syndrome and accumulating evidences suggest that lipid metabolism is as important to diabetes as carbohydrate metabolism [2]

  • High serum levels of fatty acid synthase (FAS) have been detected in patients with chronic hepatitis viral infections and circulating FAS concentration correlated with the degree of liver steatosis [10]

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Summary

Introduction

Liver steatosis may be considered the consequence of an increased influx of free fatty acids or a decreased export of lipids through very low density lipoprotein (VLDL), less fatty acid oxidation or increased de novo lipogenesis in the liver [1]. FAS expression appears to play an important role in the growth and neoplastic transformation of colonic mucosa [12,13]. Our previous study demonstrated that FAS activity levels, as well as the expression of its mRNA are up-regulated in colorectal cancer tissues compared with “normal” surrounding mucosa [13]. FAS is a key enzyme in de novo lipogenesis and both FAS gene expression and enzymatic activity are primarily regulated by metabolic signals in the liver. Lipoprotein lipase (LPL), the rate-limiting enzyme for the hydrolysis of core triglycerides, plays a pivotal role in lipid metabolism. This study aims to investigate if circulating levels of FAS and LPL could be clinically associated with liver steatosis

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