Triglycerides May Explain Cognition Problems in Obesity
Obese mice performed more poorly in tests; triglyceride-lowering drug improved performance
FRIDAY, April 25 (HealthDay News) -- Experiments with mice suggest that triglycerides play a major role in obesity-related cognitive disturbance and that lowering triglycerides can improve such impairment, according to research published in the May issue of Endocrinology.
Susan A. Farr, Ph.D., of the Saint Louis University School of Medicine in St. Louis and colleagues describe their work comparing the performance of obese and normal-weight mice in a variety of tests. Obese mice were impaired in a T-maze shock avoidance test, a spatial water maze test and a food reward lever test.
Obese mice treated with the triglyceride-lowering drug gemfibrozil performed better in the T-maze. Injecting the triglyceride triolein into the brains of mice of normal weight resulted in poorer performance than that of mice receiving saline or the free fatty acid palmitate.
"The mechanism(s) by which high triglyceride levels impair memory remain unclear, but our results suggest interesting possibilities. Acyl-CoA/free fatty acids and linoleic derivatives are capable of modifying glutamate release. Our work would suggest that triglycerides also affect the NMDA calcium channel. Oxidative stress may play a role as obesity itself is a proinflammatory, oxidatively stressed state," the authors write. "Activation of the NMDA channel can lead to increased ROS species and release nitric oxide. Finally, nitric oxide and ROS can act synergistically to increase oxidative stress and damage. Therefore, obesity-induced oxidative stress could disrupt superoxide signaling in hippocampal neurons, with the resultant synaptic dysfunction accounting for impaired cognitive function."