The Role Of L-FABP And FATP4 In The Development Of NAFL In Rat

Aims: The role of the liver-derived fatty acid binding protein (L-FABP) and the fatty acid transport protein 4(FATP4) in the development of rat non-alcoholic fatty liver (NAFL) will be investigated and the possible mechanisms of pathogenesis will be further discussed with respect to the metabolisms of the fatty acid.Methods: Forty male Wistar rats were randomly divided into two groups designated as group C as normal control and group F in which rats were given fatty chew. The body weight, the level of triglyceride (TG) and malondialdehyde (MDA) in liver tissue and the level of TG ,free fatty acid (FFA) and ALT in the serum were measured at week 2, 4,8 and 12. The mRNA expressions of L-FABP, FATP4 and acyl-coA synthetase (ACS) in rat liver were detected by RT-PCR. The localization and protein level of L-FABP and FATP4 in liver tissue were further evaluated with immunohistochemistry and/or Western blot along with the study of histology and ultra structure of liver during the course of the experiment.Results: The body weights of the rats in group F were significantly greater than those in group C at any given time point (P<0.05 for week 2 and P<0.01 for week 4,8and 12). The histology of the rat liver in group F revealed fatty degeneration of hepatocytes at week 4 and advanced to moderate or even severe fatty liver at week 8 and 12 respectively, while those in group C remained normal. The level of the TG and MDA in the liver tissue started to increase at week 4 and kept going up at later time point in group F and statistically higher than that in group C (P<0.01). The level of FAA and TG in the serum of the rats in group F also increased at week 4 and significantly higher than that in group C at week 8 and 12(P<0.01). The serum ALT was starting increase at week 8 and reached at its peak at week 12(P<0.01). The hepatocytes were stained in cytoplasm with antibody against L-FABP while the membranous staining was observed in hepatocytes with antibody against FATP4. The staining intensity of hepatocyte with both antibodies was much darker in group F. The expression of FATP4, L-FABP mRNA and its protein detected by RT-PCR and Western blot were all starting increase at week 2 and reached at their peak at week 12 in group F, and they were significantly different from group C (P<0.05). However, no difference of ACS mRNA expression was observed between two groups at any time points (P>0.05).Conclusion: (l)The high fat food can induce and promote the expression of L-FABP and FATP4. The significant alteration of these genes expression occurs earlier even without obvious pathological change seen in the liver tissue. (2)The mRNA and/or protein level of L-FABP and FATP4 in heaptocytes were increased during of the development of NAFL in rat. (3)L-FABPn FATP4 along with ACS in liver were closely related to fatty acid metabolism and lipid peroxidation of liver cells and might play a role in the process of NAFL.