Fig. 2

The brain’s fatty acid homeostasis is centred on astrocytes. The source of astrocyte fatty acids is the blood–brain barrier and neurons overproducing fatty acids in response to neural stimulation, which enter the cell via fatty acid transport protein (FATP), fatty acid binding protein (FABP) and apolipoprotein E, and form lipid droplets (LDs) for storage in the endoplasmic reticulum. Fatty acids are converted to fatty acyl-CoAs (FA-CoAs) by a family of acyl-CoA synthetases (ACS). Carnitine palmitoyl transferases (CPT) and carnitine-acylcarnitine translocases (CAT) translocate FA-CoAs into the mitochondrial matrix, where they participate in β-oxidation and the tricarboxylic acid (TCA) cycle. Fatty acid synthesis begins with the conversion of acetyl coenzyme A to malonyl coenzyme A, which is then extended to form C16:0-CoA, a reaction that requires the participation of acetyl coenzyme A carboxylases (ACCs), ATP citrate lyase (ACLY), and fatty acid synthase (FASN).Subsequent elongation and desaturation steps, catalysed by elongases (ELOVL1-7) and desaturases (Δ4,5,6,9D), form fatty acids of different carbon lengths and degrees of saturation. Ketone bodies, an intermediate product of fatty acid metabolism in astrocytes, can be transported via monocarboxylate transporter proteins (MCT) to supply energy to neurons. Microglia also perform part of the function of consuming excess fatty acids in the brain. Fatty acids produced by astrocytes may be transported to at least synaptic glial cells to participate in myelin formation or myelin regeneration