How microglial ER Stress may lead to obesity
Endoplasmic reticulum (ER) stress is generated from chronic high-fat diet (HFD) feeding that leads to hypothalamic inflammation and systemic metabolic dysfunction.
In hypothalamic, microglia and astrocytes mediate inflammation but the role of Inositol-Requiring Enzyme 1α (IRE1α), a primary ER stress sensor, in glial cells and its contributions to metabolic dysfunction remains elusive.
Deleting IRE1α in microglia significantly reduced LPS-induced pro-inflammatory cytokine gene expression and protected male mice from HFD-induced obesity, glucose intolerance, and hypothalamic inflammation, with no metabolic benefits observed in female mice.
Male mice lacking microglial IRE1α revealed significant transcriptional reprogramming of the hypothalamus, including upregulation of genes related to mitochondrial fatty acid oxidation, metabolic adaptability, and anti-inflammatory responses.
https://www.sciencedirect.com/science/article/pii/S2212877825000353
