AI Article Synopsis
- Metabolic diseases like obesity and type 2 diabetes involve insulin resistance, particularly in neurons of the arcuate nucleus of the hypothalamus that help regulate metabolism.
- The study highlights how the perineuronal net, an extracellular matrix that surrounds these neurons, becomes altered during metabolic diseases, contributing to insulin resistance.
- Disrupting this protective net in obese mice improves brain insulin access, reverses insulin resistance in neurons, and boosts metabolic health, revealing extracellular matrix changes as critical to understanding metabolic diseases.
Article Abstract
Metabolic diseases such as obesity and type 2 diabetes are marked by insulin resistance. Cells within the arcuate nucleus of the hypothalamus (ARC), which are crucial for regulating metabolism, become insulin resistant during the progression of metabolic disease, 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424483 | PMC |
| http://dx.doi.org/10.1038/s41586-024-07922-y | DOI Listing |
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