Effects of different dietary protocols on the expression of genes coding for pro- or antioxidant enzymes in the renal cortex

Abstract

The prevalence of obesity is on the rise in many parts of the world and so obesity-related disorders such as hypertension, dyslipidemia, diabetes mellitus and atherosclerosis. These diseases are the leading causes of chronic kidney and end-stage renal diseases. The metabolic changes in obesity are associated with an increased production of reactive oxygen species (ROS) which can damage DNA, cell components and disturb cell function. This study investigates the effects of high-fat diets on the expression of genes coding for prooxidant and antioxidant enzymes in the renal cortex of male C57BL/6 mice. Furthermore, it distinguishes between a diet high in animal fat (MFD, milk fat diet) and a diet high in plant fat (COD, coconut oil diet) and investigates if the effects of the animal-fat diet are reversible by normalizing the diet. The mice were fed for 30 weeks according to the specific dietary protocol. At the end of the treatment period, mRNA expression levels of the genes of interest were measured using real-time PCR. This work shows that the intake of high-fat diet (high in animal fat or plant fat) is associated with increased mRNA expression levels of genes coding for prooxidant and inflammatory enzymes. Specifically, the NAD(P)H-oxidase subunit Nox4 and the intercellular adhesion molecule-1 (ICAM-1) showed markedly increased expression levels. Additionally, an upregulation of the antioxidant system, particularly of the glutathione peroxidase-1 (Gpx1), in all mice with a higher fat intake was detected. No significant difference between the diet high in animal fat and the diet high in plant fat on the mRNA expression levels of the investigated genes was seen. The effects of the animal fat diet are not reversible by diet normalization protocol used in this work. This study provides a possible molecular explanation for the increased oxidative stress and the increased inflammation in murine renal cortex observed after high-fat diet intake.