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 a (ACCα) in the liver from the aspect of the fatly acid synthesis pathway. Methods A total of 40 clean male Sprague - Dawley rats were given adaptive feeding for 14 days and wrere 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 — le, 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 - lest 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 (AET), 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 — PGR showed consistent protein and mRNA expression features of SREBP — lc, FAS, and ACCa, and there were significant differences in the protein and mRNA expression of REBP — lc, FAS, and ACCa 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 — lc, FAS, and ACCα in 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 — lc, FAS, and ACCα. [ABSTRACT FROM AUTHOR]