Chronic intake of moderate fat-enriched diet induces fatty liver and low-grade inflammation without obesity in rabbits.

Non-Alcoholic Fatty Liver Disease (NAFLD) is the cause of chronic liver disease. Even though NAFLD is strongly associated with obesity and metabolic syndrome, there is a proportion of patients who develop this condition in the absence of obesity and the underlying mechanisms are poorly understood. We investigated early events in the pathogenesis of non-obese NAFLD, analyzing the impact of the chronic intake of a moderate fat-enriched diet on hepatic lipid accumulation and their relationship with inflammation. Rabbits fed with a moderate Fatty-Acid- Enriched Diet 3% palmitic acid (FAED), were evaluated for body weight, biochemical parameters, and liver function. Liver samples were analyzed by histology and RT-qPCR to measure lipid accumulation, the expression of inflammation-related genes IL-1ß, IL-6, IL-10, IL-13, IL-18, COX-2, TNF-α, and TLR-4. Chronic consumption by 6-months of FAED did not generate metabolic changes, but it induced fatty liver. We also observed the development of low-grade inflammation characterized by the up regulation of TNF-α, IL-13 and IL-18. The consumption by 12-months of FAED caused the overexpression of IL-6, IL-10, IL-13, COX-2, and TLR-4. We show that hepatic steatosis is an early consequence of fat-enriched diets, and that it is accompanied by an immune response that exerts protective effects that prevent the development of metabolic disorders, such as overweight/obesity and metabolic syndrome. However, the excessive intake of fatty acids renders these mechanisms less efficient for delaying the start of metabolic alterations. Rabbits fed with FAED can be used as a model of NAFLD in non-obese and obese groups, especially at early stages of the disease.

HUVECs from newborns with a strong family history of myocardial infarction overexpress adhesion molecules and react abnormally to stimulating agents.

Atherosclerosis is a complex disease involved in major fatal events such as myocardial infarction and stroke. It is the result of interactions between metabolic, dietetic and environmental risk factors acting on a genetic background that could result in endothelial susceptibility. Our aim was to determine the patterns of expression of adhesion molecules and whether phosphatidylserine is translocated to the cell surface of human umbilical vein endothelial cells (HUVECs) isolated from healthy newborns born to parents with a strong family history of myocardial infarction under TNF-alpha or oxLDL stimulated conditions. Compared to control HUVECs, experimental cords showed: (a) a four-fold increase in VCAM-1 expression under basal conditions, which showed no change after stimulation with the pro-atherogenic factors; (b) a two-fold increase in basal P-selectin expression that reached a 10-fold increase with any of the pro-atherogenic factors; (c) a basal ICAM-1 expression similar to P-selectin that was not modified by the pro-atherogenic molecules; (d) a similar PECAM-1 expression. Unexpectedly, phospathidylserine expression in experimental cord HUVECs was significantly increased (211 817 versus 3354 TFU) but was not associated to apoptotic death as the percentage of dead cells induced by TNF-alpha treatment was very low (0.55 versus 9.87% in control HUVECs). The latter result was corroborated by TUNEL staining. T cell adherence to HUVECs was highly up-regulated in the genetically predisposed samples. The analysis of nonpooled HUVECs, from newborns to family predisposed myocardial-infarction individuals, might represent a useful strategy to identify phenotypical and functional alterations, and hopefully, to take early preventive actions.