Iron overload potentiates diet-induced hypercholesterolemia and reduces liver PPAR-α expression in hamsters

Iron stores and lipids are related to the development of cardiovascular disease. Given that peroxisome proliferator-activated receptor alpha (PPAR-a) regulates important physiological processes that impact lipid and glucose homeostasis, we decided to investigate the effects of iron overload on serum lipids and the liver expression of PPAR-a, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and cholesterol 7a-hydroxylase. Hamsters were divided into four groups. The standard group (S) was fed the AIN-93M diet, the SI group was fed the diet and iron injections, the hypercholesterolemic group (H) was fed a standard diet containing cholesterol, and the HI group was fed a high-cholesterol diet and iron injections. Serum cholesterol in the HI group was higher than in the H group. Gene expression analysis of PPAR-a showed that the HI group had a lower PPAR-a expression than H. These data show that iron, when associated with a high-fat diet, can cause increased serum cholesterol levels, possibly due to a reduction in PPAR-a expression. (c) 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:224229, 2012; View this article online at . DOI 10.1002/jbt.21410