Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α.

Obesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, and higher risk of developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate the effects of palmitate, a saturated fatty acid present at high amounts in fat-rich diets, in the brain. Palmitate is increased in the cerebrospinal fluid (CSF) of overweight and obese patients with amnestic mild cognitive impairment. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Palmitate induces astroglial and microglial activation in the mouse hippocampus, and its deleterious impact is mediated by microglia-derived tumor necrosis factor alpha (TNF-α) signaling. Our results establish that obesity is associated with increases in CSF palmitate. By defining a pro-inflammatory mechanism by which abnormal levels of palmitate in the brain impair memory, the results further suggest that anti-inflammatory strategies may attenuate memory impairment in obesity.

Removal of 14-C-palmitate during ventriculocisternal perfusion in conscious dogs in insulin-induced hypoglycemia.

A detailed description of a method is presented allowing continous ventriculocisternal perfusion of metabolites in the conscious dog. Using this preparation, the loss of the infused albuminbound 14-C-aplmitate, was studied in 14 conscious dogs during ventriculocisternal perfusion with artificial cerebrospinal fluid (CSF). Forty-five percent of the infused 14-C-palmitate was recovered from the cisternal effluent under equilibrium conditions after 60 min of perfusion. The effect of the injection of 2.0 U insulin/kg was also investigated in seven dogs. Plasma glucose concentration decreased to 40--50 mg% and the amount of 14-C-palmitate recovered was significantly higher one hour after insulin compared to the controls receiving saline injections. No significant changes in cerebral arteriovenous differences of glucose or oxygen or in venous 14-C-palmitate concentration were observed during the same time. It is concluded that the combined use of ventriculocisternal perfusion and the analysis of cerebral arteriovenous differences are useful in studying brain metabolism in the consciuos dog.