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 Shimizu; 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

doi:10.1016/j.celrep.2021.109362

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

Cell Rep. 2021 Jul 13;36(2):109362. doi: 10.1016/j.celrep.2021.109362.

Authors

Sara Kohnke¹, Sophie Buller¹, Danae Nuzzaci¹, Katherine Ridley², Brian Lam¹, Helena Pivonkova³, Marie A Bentsen⁴, Kimberly M Alonge⁴, Chao Zhao⁵, John Tadross¹, Staffan Holmqvist², Takahiro Shimizu⁶, Hannah Hathaway⁷, Huiliang Li⁶, Wendy Macklin⁷, Michael W Schwartz⁴, William D Richardson⁶, Giles S H Yeo¹, Robin J M Franklin⁵, Ragnhildur T Karadottir³, David H Rowitch⁸, Clemence Blouet⁹

Affiliations

¹ MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK.
² Department of Paediatrics and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
³ Wellcome-MRC Cambridge Stem Cell Institute, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
⁴ University of Washington Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA.
⁵ Wellcome-MRC Cambridge Stem Cell Institute, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁶ Wolfson Institute for Biomedical Research, University College London, London, UK.
⁷ Department of Cell & Developmental Biology and Program in Neuroscience, University of Colorado School of Medicine, Aurora, CO, USA.
⁸ 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.
⁹ MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address: [email protected].

Abstract

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.

Keywords: energy balance; glucose homeostasis; hypothalamus; median eminence; nutrition; obesity; oligodendrocyte; perineuronal nets; plasticity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Cell Differentiation*
Cell Lineage
Cell Proliferation
Humans
Male
Mechanistic Target of Rapamycin Complex 1 / metabolism
Median Eminence / cytology*
Mice
Mice, Inbred C57BL
Nerve Net / physiology*
Nutritional Physiological Phenomena*
Oligodendroglia / cytology*
Oligodendroglia / ultrastructure
Single-Cell Analysis
Transcriptome / genetics

Substances

Mechanistic Target of Rapamycin Complex 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding