Resumen de Sex-dependent effect of liver growth factor on atherosclerotic lesions and fatty liver disease in apolipoprotein E knockout mice
Joaquín C. Surra Muñoz, Natalia Guillén, Cristina Barranquero, José M. Arbonés Mainar, María Ángeles Navarro, Sonia Gascón, Carmen Arnal, J. Godino, Mario A. Guzmán, Juan J Díaz-Gil, Jesús de la Osada García
Objective: Since the hepatic mitogen, liver growth factor (LGF), improves vascular structure and function in a hypertensive rat model and exhibits antioxidant activity, it may play a role in the development of atherosclerosis. Methods: To test this hypothesis, 14 male and 11 female apolipoprotein E (apoE)-deficient mice with a C57BL/6J genetic background were injected intraperitoneally twice a week with 1.7 µg of LGF per mouse for ten weeks. Plasma carbohydrates, inflammatory and lipid parameters, apolipoproteins A-I and A-II and paraoxonase activity were assessed at the end of the experimental period. Histological and chemical nalyses of the livers and quantification of aortic atherosclerotic lesions were also carried out. Results: LGF administration changed neither plasma lipid nor inflammatory parameters. ApoA-I and arylesterase activity were not affected by LGF either, while apoA-II decreased significantly in males but not in females. Plasma apoA-II correlated positively with liver fat in males but negatively in females. Atherosclerotic area lesions in males receiving LGF were 25% lower thain in control mice. Likewise, a significant reduction of fatty liver disease was also observe in males in association with decreased levels of insulin, leptin and resistin. Conclusion: These results indicate that administartion of LGF modulates atherosclerotic lesions in a sex-dependent manner. This effect is independent of plasma cholesterol, triglycerides, IL-6, MCP-1 and TNF-a and is related to a remodelling of HDL particles characterised by a decrease in apoA-II induce by changes in hepatic mRNA expression. Hence, LGF administration could be used as a safe alternative to control fatty liver disease and atherosclerosis in males.
