Abstract
Regulation of EGF receptor binding and autophosphorylation were investigated in high-fat (HF) fed rats in comparison with the insulin receptor. EGF binding to hepatic microsomal membranes (MP) was lower in HF-fed rats than in the controls (36.9±6.6 vs 59.9±6.2%). Scatchard analysis revealed that this was due to a decreased number of receptors (936±141 vs 1795±119pM). A HF diet did not affect insulin binding to purified receptor preparations (RP) from liver, but did decrease the insulin binding affinity of MPs. Autophosphorylation of EGF receptors in both MPs and RPs of the HF group were significantly reduced to almost 40% of control levels throughout the entire dose-response curve when adjusted for protein concentration (Control 49.6±3.1 vs HF 20.2±2.9f moles/150μg/10min at 420nM of EGF). When adjusted for receptor number, the difference in EGF receptor autophosphorylation in the HF and control group was not statistically significant. Autophosphorylation of insulin receptors was decreased to almost 50% in HF-fed rats when adjusted not only for the amount of protein but receptor number.
In summary, a HF diet caused a decrease in EGF receptor number, but EGF receptor kinase was unaffected. On the other hand, while the HF diet did not affect insulin receptor number, it did decrease insulin receptor kinase activity. These findings suggest that changes in EGF receptors differ from those in insulin receptors under high-fat alimentation conditions.
