Researchers uncover how the buildup of extracellular matrix proteins and sugars prevents insulin from reaching hunger-regulating neurons, leading to disrupted metabolism and increased risk of obesity. In a recent study published in Nature , researchers reveal a novel mechanism by which hypothalamic inflammation drives fibrotic remodeling in perineuronal nets (PNNs), a specialized extracellular matrix (ECM) of the hypothalamic arcuate nucleus (ARC), to induce metabolic dysfunction. Background Elevated blood glucose levels trigger beta cells of the pancreas to release more insulin.
This hormone circulates to the ARC, which controls physiological processes. A loss of insulin sensitivity increases dietary intake, leading to fat accumulation and obesity. The ECM, a network of proteins and sugars, disrupts insulin's reach to hunger-regulating ARC neurons, contributing to obesity.
The ECM is a dynamic structure essential for tissue function. However, pathological changes can lead to increased fibrosis in the ECM in the form of perineural nets surrounding the Agouti-Related Protein (AgRP)-releasing neurons within the ARC of the hypothalamus. The fibrotic buildup prevents insulin activity.
Studies report that insulin resistance can result in metabolic diseases like obesity and insulin-independent diabetes. About the study The present study investigated the remodeling of the ARC extracellular matrix in metabolic diseases such as obesity. Researchers fed mice regular chow or high-fat, h.