Effects of a high-fat diet on expression of the hypothalamic NADPH oxidases

Abstract

Background and Aims - Obesity is an increasing epidemic worldwide; therefore, numerous clinical and basic studies focus on the potential mechanisms underlying this complex disorder. High-fat (HF) diet-induced obesity is associated with mild inflammation in peripheral tissues. NADPH oxidases (NOX) are recognized as a physiological source of reactive oxygen species (ROS) contributing to the inflammation. Previous studies proposed that similar events may also occur in the hypothalamus, a cerebral area responsible for the regulation of energy homeostasis. Purpose of this study was to examine the effects of a HF diet on expression of the hypothalamic NADPH oxidases. We also examined expression of transcription factor HIF-1alpha (HIF-1α) owing to its potential involvement in the upregulation of the NOX system. Methods - Male rats were placed on HF diet starting at 9 weeks of age and lasting for 12 weeks. Expression of NOX 2/gp91phox, NOX 4, p22phox subunit, and HIF-1α in the hypothalamus was evaluated by Western blot analysis. Results - The HF diet significantly increased the expression of NOX 4 and its p22phox subunit in the hypothalamus. No significant changes in the levels of NOX 2 and HIF-1α were observed. Conclusions – The present study suggests that NOX 4 but not NOX 2, might be involved in the onset of the hypothalamic inflammation underlying the HF diet-induced obesity. The involvement of HIF-1α needs to be further investigated.