The brain is an important organ that controls systemic pathologies, while also receiving various regulatory signals from the periphery via the endocrine and autonomic nervous. Glial cells, which abundantly surround neurons in the brain, are known to play diverse roles by monitoring structural and functional changes in the central nervous system and dynamically transforming their morphology and function according to their surroundings. Recent basic studies have revealed that there are many subsets of glial cells that specifically transform in response to various diseases. Cancer cachexia affects many patients with terminal cancer and significantly reduces their quality of life. We hypothesized that the systemic multiorgan dysfunction observed in cancer cachexia may be triggered by brain dysfunction, especially glial cell transformation, and attempted to analyze hypothalamic glial cell transformation under the pathology of cancer cachexia. We found that the gene expression profile of hypothalamic glial cells in cancer cachexia was dramatically altered in response to increased levels of inflammatory cytokines and endotoxins in the periphery. These finding suggest that altered function of glial cells may trigger systemic dysfunction, such as feeding and immune compromise, through interactions with neurons.