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

The mediobasal hypothalamus (arcuate nucleus, 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 (PNN), emerging regulators of ARH metabolic functions, are rapidly remodelled, 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 remodelling are blunted, and enzymatic digestion of local PNN increases food intake and weight gain. We conclude that MBH PNN are required for the maintenance of energy balance in lean mice and are remodelled in the adult ME via the nutritional control of oligodendrocyte differentiation