Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence
Sara Kohnke,
Sophie Buller,
Danae Nuzzaci,
Katherine Ridley,
Brian Lam,
Helena Pivonkova,
Marie A. Bentsen,
Kimberly M. Alonge,
Chao Zhao,
John Tadross,
Staffan Holmqvist,
Takahiro Shimizo,
Hannah Hathaway,
Huiliang Li,
Wendy Macklin,
Michael W. Schwartz,
William D. Richardson,
Giles S.H. Yeo,
Robin J.M. Franklin,
Ragnhildur T. Karadottir,
David H. Rowitch,
Clemence Blouet
Affiliations
Sara Kohnke
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK
Sophie Buller
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK
Danae Nuzzaci
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK
Katherine Ridley
Department of Paediatrics and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
Brian Lam
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK
Helena Pivonkova
Wellcome-MRC Cambridge Stem Cell Institute, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
Marie A. Bentsen
University of Washington Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA
Kimberly M. Alonge
University of Washington Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA
Chao Zhao
Wellcome-MRC Cambridge Stem Cell Institute, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
John Tadross
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK
Staffan Holmqvist
Department of Paediatrics and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
Takahiro Shimizo
Wolfson Institute for Biomedical Research, University College London, London, UK
Hannah Hathaway
Department of Cell & Developmental Biology and Program in Neuroscience, University of Colorado School of Medicine, Aurora, CO, USA
Huiliang Li
Wolfson Institute for Biomedical Research, University College London, London, UK
Wendy Macklin
Department of Cell & Developmental Biology and Program in Neuroscience, University of Colorado School of Medicine, Aurora, CO, USA
Michael W. Schwartz
University of Washington Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA
William D. Richardson
Wolfson Institute for Biomedical Research, University College London, London, UK
Giles S.H. Yeo
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK
Robin J.M. Franklin
Wellcome-MRC Cambridge Stem Cell Institute, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
Ragnhildur T. Karadottir
Wellcome-MRC Cambridge Stem Cell Institute, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
David H. Rowitch
Department of Paediatrics and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Wolfson Institute for Biomedical Research, University College London, London, UK
Clemence Blouet
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK; Corresponding author
Summary: 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.
