Influence of low-level lead exposure on liver function and blood lipids in rats with nonalcoholic fatty liver disease

Objective To investigate the influence of low-lead high-fat diet on liver function and blood lipids in rats with nonalcoholic fatty liver disease ( NAFLD) , as well as the expression of sterol regulatory element-binding protein-1 c ( SREBP-1 c) , fatty acid synthase ( FAS) , and acetyl-CoA carboxylase α ( ACCα) in the liver from the aspect of the fatty acid synthesis pathway. Methods A total of 40 clean male Sprague-Dawley rats were given adaptive feeding for 14 days and were then randomly divided into normal group, low-lead exposure group, high-fat diet group, and low-lead high-fat diet group, with 10 rats in each group. The rats were sacrificed after 8 weeks of feeding with the corresponding diet, and serum and liver samples were collected to measure blood lead, liver function, blood lipids, and liver pathology. Western blot and RT-PCR were used to measure the protein and mRNA expression of SREBP-1 c, FAS, and ACCα involved in fatty acid synthesis. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results There were marked liver pathological changes after exposure. The sections from the normal group and the low-lead exposure group had a smooth surface and evenly distributed nuclei, without marked adipocyte infiltration or inflammatory response; the sections from the low-lead high-fat diet group and the high-fat diet group had marked fatty infiltration and inflammatory cell infiltration, and those from the low-lead high-fat diet group had larger fat vacuoles. There were significant differences in blood lead and liver lead between groups ( F = 37. 792 and 21. 458, both P < 0. 001) , and the low-lead exposure group and the low-lead high-fat diet group had significantly higher levels than the normal group ( all P < 0. 05) . There were significant differences in aspartate aminotransferase ( AST) , alanine aminotransferase ( ALT) , high-density lipoprotein cholesterol ( HDL-C) , and low-density lipoprotein cholesterol ( LDL-C) between groups ( F = 35. 791, 24. 422, 37. 287, and 42. 371, all P <0. 001) , and the low-lead exposure group, the high-fat diet group, and the low-lead high-fat diet group had significantly higher AST, ALT, LDL-C, and HDL-C than the normal group ( all P < 0. 05) . Western blot and RT-PCR showed consistent protein and mRNA expression features of SREBP-1 c, FAS, and ACCα, and there were significant differences in the protein and mRNA expression of REBP-1 c, FAS, and ACCα between groups ( protein expression: F = 21. 864, 22. 358, and 57. 761, all P < 0. 001; mRNA expression: F =34. 652, 22. 964, and 42. 384, all P < 0. 001) . Compared with the normal group and the low-lead exposure group, the high-fat diet group and the low-lead high-fat diet group had significant increases in the protein and mRNA expression of SREBP-1 c, FAS, and ACCαin the liver ( all P < 0. 05) . Conclusion Low-lead exposure can aggravate liver function and dyslipidemia in NAFLD rats, possibly by regulating the expression of SREBP-1 c, FAS, and ACCα.