Specific Aim #1: To determine the occurrence of neuronal mitochondrial dysfunction in male rats with neuronal insulin resistance caused by the consumption of long-term HF diet via measuring ROS, cytochrome C, mitochondrial swelling, mitochondrial membrane potential and mitochondrial nitric oxide syntheses (mtNOS) in neuronal mitochondria of both HF-diet and normal diet-fed rats.
Specific Aim #2: To determine whether the administration of PPAR-gamma agonist, rosiglitazone, into male rats with neuronal insulin resistance induced by long term HF diet consumption can improve the neuronal insulin resistance, by increasing neuronal insulin receptor function (insulin-induced LTD), neuronal insulin signaling and neuronal mitochondrial function
Specific Aim 3: To determine whether the administration of estrogen into both genders of animals with neuronal insulin resistance induced by HF diet consumption can improve the neuronal insulin resistance condition by increasing neuronal insulin receptor function in hippocampus (insulin-induced LTD), neuronal insulin signaling and improving neuronal mitochondrial function.
Specific Aim 4: To determine whether PPAR agonist administration in long term HF-fed ovariectomized (female) rats can improve neuronal insulin resistance by increasing neuronal insulin receptor function in hippocampus (insulin-induced LTD), neuronal insulin signaling and neuronal mitochondrial function.
