Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence

The mediobasal hypothalamus (MBH; arcuate nucleus of the hypothalamus [ARH] and median eminence [ME]) is a key nutrient sensing site for the production of the complex homeostatic feedback responses required for the maintenance of energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation and differentiation of oligodendrocyte progenitors, leading to the production of new oligodendrocytes in the ME specifically. During this nutritional paradigm, ME perineuronal nets (PNNs), emerging regulators of ARH metabolic functions, are rapidly remodeled, and this process requires myelin regulatory factor (Myrf) in oligodendrocyte progenitors. In genetically obese ob/ob mice, nutritional regulations of ME oligodendrocyte differentiation and PNN remodeling are blunted, and enzymatic digestion of local PNN increases food intake and weight gain. We conclude that MBH PNNs are required for the maintenance of energy balance in lean mice and are remodeled in the adult ME by the nutritional control of oligodendrocyte differentiation. [Display omitted] •The median eminence contains a dense population of newly formed oligodendrocytes•Nutritional signals regulate oligodendrocyte differentiation in the median eminence•Oligodendrocyte plasticity in the median eminence regulates local perineuronal nets Kohnke et al. find that median eminence oligodendrocyte proliferation and differentiation uniquely respond to nutritional signals, revealing the plasticity of this cell type. They directly implicate adult-born oligodendrocytes in the regulation of local perineuronal nets,and show that these extracellular structures modulate the control of energy balance.