Exploring the potential hypothalamic role in mediating cisplatin-induced negative energy balance

Cisplatin is a chemotherapeutic drug commonly used for treating different types of cancer. However, long-term use can lead to side effects, including anorexia, nausea, vomiting, and weight loss, which negatively affect the patient's quality of life and ability to undergo chemotherapy. This study aimed to investigate the mechanisms underlying the development of a negative energy balance during cisplatin treatment. Mice treated with cisplatin exhibit reduced food intake, body weight, and energy expenditure. We observed altered neuronal activity in the hypothalamic nuclei involved in the regulation of energy metabolism in cisplatin-treated mice. In addition, we observed activation of microglia and inflammation in the hypothalamus following treatment with cisplatin. Consistent with this finding, inhibition of microglial activation effectively rescued cisplatin-induced anorexia and body weight loss. The present study identified the role of hypothalamic neurons and inflammation linked to microglial activation in the anorexia and body weight loss observed during cisplatin treatment. These findings provide insight into the mechanisms underlying the development of metabolic abnormalities during cisplatin treatment and suggest new strategies for managing these side effects. [Display omitted] •Cisplatin induces negative energy balance.•Cisplatin leads to altered neuronal activity in hypothalamic arcuate nucleus.•Cisplatin elevates the inflammatory response in hypothalamic microglial cells.•The activation of microglia is accountable for the sickness response triggered by cisplatin treatment.•Minocycline treatment reverses the sickness responses induced by cisplatin.