Projects per year
Abstract
Metabolic diseases such as obesity and type 2 diabetes are marked by insulin resistance 1,2. Cells within the arcuate nucleus of the hypothalamus (ARC), which are crucial for regulating metabolism, become insulin resistant during the progression of metabolic disease 3–8, but these mechanisms are not fully understood. Here we investigated the role of a specialized chondroitin sulfate proteoglycan extracellular matrix, termed a perineuronal net, which surrounds ARC neurons. In metabolic disease, the perineuronal net of the ARC becomes augmented and remodelled, driving insulin resistance and metabolic dysfunction. Disruption of the perineuronal net in obese mice, either enzymatically or with small molecules, improves insulin access to the brain, reversing neuronal insulin resistance and enhancing metabolic health. Our findings identify ARC extracellular matrix remodelling as a fundamental mechanism driving metabolic diseases.
Original language | English |
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Pages (from-to) | 914-922 |
Number of pages | 9 |
Journal | Nature |
Volume | 633 |
Issue number | 8031 |
Early online date | 18 Sept 2024 |
DOIs | |
Publication status | Published - 26 Sept 2024 |
Bibliographical note
Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Projects
- 2 Active
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NHMRC Ideas led by UoM: Reversing Neurofibrosis: A New Way to Treat Type-2 Diabetes
Dodd, G., Ling, C., Moh, E., Daglas, M., Boskovic, Z., Sumithran, K., Cho, E., Rose, A. & Packer, N.
1/01/23 → 31/12/26
Project: Research
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COESB: ARC Centre of Excellence in Synthetic Biology
Paulsen, I., Filipovska, A., Parker, R., Nielsen, L. K., Neilan, B. A., Alexandrov, K., Jackson , C., Wodak, J., Rackham, O., Marcellin, E., Gillings, M., Rogers, W., Lee, L., Packer, N., O'Hara, I. M., Speight, R., Vickers, C. E., Beliaev, A., Scott, C., Lacey, J., Mankad, A., Calvert, J., Thomas, G., Rodriguez-Concepcion, M., Fleishman, S., Koepke, M., Ball, M., Turner, N. J., Borneman, A. R., Holowko, M., Goold, H., Ellis, T., Mitchell, L. A. & Dai, J.
9/11/20 → 8/11/27
Project: Research