Tanycytes and a differential fatty acid metabolism in the hypothalamus

Although the brain controls all main metabolic pathways in the whole organism, its lipid metabolism is partially separated from the rest of the body. Circulating lipids and other metabolites are taken up into brain areas like the hypothalamus and are locally metabolized and sensed involving several hypothalamic cell types. In this study we show that saturated and unsaturated fatty acids are differentially processed in the murine hypothalamus. The observed differences involve both lipid distribution and metabolism. Key findings were: (i) hypothalamic astrocytes are targeted by unsaturated, but not saturated lipids in lean mice; (ii) in obese mice labeling of these astrocytes by unsaturated oleic acid cannot be detected unless β-oxidation or ketogenesis is inhibited; (iii) the hypothalamus of obese animals increases ketone body and neutral lipid synthesis while tanycytes, hypothalamic cells facing the ventricle, increase their lipid droplet content; and (iv) tanycytes show different labeling for saturated or unsaturated lipids. Our data support a metabolic connection between tanycytes and astrocytes likely to impact hypothalamic lipid sensing. GLIA 2017;65:231-249.