DHA upregulates FADS2 expression in primary cortical astrocytes exposed to vitamin A.

The fads2 gene encoding delta6-desaturase, the rate-limiting enzyme of the LCPUFA biosynthesis is expressed in astrocytes. Dietary fatty acids, which cross the blood-brain barrier, may regulate the transcription of lipogenic enzymes through activation of transcription factors such as peroxisome proliferator-activated receptors (PPARs). The PPARs form the transcription complex with retinoid X receptors (RXRs) that are activated by 9-cis retinoic acid, a metabolite of vitamin A (VA). The study examines whether challenge of astrocytes with VA, prior 24-h treatment with palmitic acid (PA), alpha-linolenic acid (ALA) or docosahexaenoic acid (DHA) has the effect on the FADS2 expression. RT-qPCR showed that in astrocytes not challenged with VA, PA increased fads2 gene expression and DHA decreased it. However, in VA-primed astrocytes, PA doubled the FADS2 mRNA levels, while DHA increased fads2 gene expression, oppositely to non-primed cells. Furthermore, similar changes were seen in VA-primed astrocytes with regard to delta6-desaturase protein levels following PA and DHA treatment. ALA did not have any effect on the FADS2 mRNA and protein levels in either VA-primed or non-primed astrocytes. These findings indicate that in the presence of vitamin A, DHA upregulates fads2 gene expression in astrocytes.

Evidence for a direct central anorectic effect of tumor-necrosis-factor-alpha in the rat.

This study was designed to investigate the effect of tumor necrosis factor-alpha (TNF) on the control of food intake in rat. The specific aims were: a) to evaluate the effects of central (ICV) or peripheral (IP) microdoses of TNF on food intake; b) to show that the TNF-induced anorexia results from a direct action of the mediator on the central nervous system; c) to demonstrate that the anorexic activity of TNF is not due to nonspecific malaise. In the first experiment, ICV administration (0.5-4.0 micrograms) of recombinant-murine tumor necrosis factor-alpha (rmTNF) significantly reduced food intake in a dose-dependent manner. The maximal effect (-66%) was observed 5 h after a 4.0 micrograms dose. In contrast, rm TNF did not affect feeding behavior when injected IP, indicating that the anorexic activity was centrally mediated. The estimated DE50 was 2.0 micrograms/rat by the ICV route. In the second experiment, the place conditioning paradigm was used to show that TNF administered ICV at 2.0 micrograms/rat did not induce aversive or deleterious effects as compared to naltrexone given IP at the equi-anorectic dose 5.0 mg/kg. It was concluded that TNF reduces food intake in rats by a direct action on the central nervous system.