New research reveals how extracellular matrix (ECM) buildup in the brain’s hypothalamus leads to insulin resistance, paving the way for innovative therapies targeting obesity and diabetes. Study: Pathogenic hypothalamic extracellular matrix promotes metabolic disease . Image Credit: Sebastian Kaulitzki / Shutterstock In a recent study published in the journal Nature , researchers reported that pathogenic hypothalamic extracellular matrix (ECM) remodeling within the hypothalamus, specifically around neurons in the arcuate nucleus (ARC), promotes metabolic disease.
Insulin resistance is closely linked to ECM remodeling in peripheral tissues, where fibrosis (excess ECM deposition) impairs insulin signaling and action. Conventionally, fibrosis was believed to only occur in peripheral tissues. Nevertheless, increasing evidence indicates that ECM remodeling can also occur in the brain, particularly in the hypothalamus, and has been observed in severe neurological diseases and after acute brain injury.
Recent reports suggest the formation of a unique ECM subtype, perineuronal nets (PNNs), around neurons expressing agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC). These PNNs serve as a regulatory barrier that controls the excitability of neurons by binding to extracellular molecules. PNN formation influences AgRP function, as its loss results in higher fiber density and changes in cell numbers.
The study and findings In the present study, researchers r.