DHA (omega-3 fatty acid) and estradiol: key roles in regional cerebral glucose uptake

Abstract

Neurons have a high energy need, requiring a continuous supply of glucose from the blood. Tight regulation of glucose metabolism in response to stimuli is essential for brain physiology. Glucose metabolism and cerebral blood flow are closely coordinated during neuronal activity to maintain proper brain function. Glucose uptake across the blood-brain barrier is facilitated by a carrier protein: the GLUT-1 transporter. The first way the body meets urgent demand for glucose is to increase the blood flow through vasodilatory responses generated by nitric oxide. If that is insufficient, the second way is to increase the density of GLUT-1 through the translocation of this transporter from intracellular stores. The third pathway is to increase GLUT-1 synthesis by stimulating SLC2A1 (GLUT-1 gene) transcription. A tandem of two key molecules, free estradiol and DHA, is involved in this critical regulation. Their relationship is synergistic and reciprocal: free estradiol with genomic and non-genomic actions via ERα, and DHA via the PPARα-RXRα and PPARɣ-RXRα heterodimers. We highlight several original mechanisms linking two main principles (neuronal stimulation and brain energy metabolism) with the fundamental roles played by DHA and free estradiol. In particular, it has been shown that from a certain level of chronic DHA deficiency, a permanent imbalance sets in with disturbances in glucose intake and brain metabolism. This DHA deficiency is an aggravating factor in some neuropathologies.