Sustained feeding of a diet high in fat resulted in a decline in the liver's insulin-degrading enzyme levels in association with the induction of oxidative and endoplasmic reticulum stress in adult male rats: Evaluation of 4-phenylbutyric acid

Abstract

The current study explored the impact of high fat diet (HFD) on hepatic oxidative and endoplasmic reticulum (ER) stress and its insulin degrading enzyme (IDE) content with the injection of 4-phenyl butyric acid (4-PBA) in adult male rats. Following the weaning period, male offspring were distributed among six distinct groups. The corresponding diet was used for 20 weeks, subsequently 4-PBA was administered for three consecutive days. Plasma glucose and insulin levels, HOMA-beta (homeostasis model assessment of beta-cell), hepatic ER and oxidative stress biomarkers and IDE protein content were assessed. Long-term ingestion of HFD (31 cow butter) induced oxidative and ER stress in the liver tissue. Accordingly, a rise in the malondialdehyde (MDA) content and catalase enzyme activity and a decrease in the glutathione (GSH) content were detected within the liver of the HFD and HFD + DMSO groups. Consumption of this diet elevated the liver expression of binding immunoglobulin protein (BIP) and C/enhancer-binding protein homologous protein (CHOP) levels while reduced its IDE content. The HOMA-beta decreased significantly. The injection of the 4-PBA moderated all the induced changes. Findings from this study indicated that prolonged HFD consumption led to a reduction in plasma insulin levels, likely attributed to pancreatic beta cell malfunction, as evidenced by a decline in the HOMA-beta index. Also, the HFD appears to have triggered oxidative and ER stress in the liver, along with a decrease in its IDE content.