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
Fateme Binayi,
Behnam Saeidi,
Fatemeh Farahani,
Mina Sadat Izadi,
Farzaneh Eskandari,
Fariba Azarkish,
Mohammad Sahraei,
Rasoul Ghasemi,
Fariba Khodagholi,
Homeira Zardooz
Affiliations
Fateme Binayi
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Behnam Saeidi
Protein Research Center, Shahid Beheshti University, Tehran, Iran
Fatemeh Farahani
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Mina Sadat Izadi
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Farzaneh Eskandari
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Fariba Azarkish
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mohammad Sahraei
School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Rasoul Ghasemi
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Fariba Khodagholi
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Homeira Zardooz
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Corresponding author. Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, POBox: 19615-1178 Tehran, Iran.
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-β (homeostasis model assessment of β-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-β 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 β cell malfunction, as evidenced by a decline in the HOMA-β index. Also, the HFD appears to have triggered oxidative and ER stress in the liver, along with a decrease in its IDE content.
