Hepatic mitochondrial function and brain tumours

Therapeutic advances remain modest for patients with malignant brain tumours, due in part to inadequate ability of in-vitro models to mimic the consequences of tumour progression in vivo, which include profound immunosuppression, cytokine dysregulation and microvascular proliferation. This review summarizes recent findings on the wasting consequences of glioma growth, including changes in hepatic metabolism caused by the tumour.

Release of proinflammatory cytokines by gliomas leads to anorexia, a sensation of tiredness and fatigue associated with sleep deprivation. The cachexia and associated decrease in relative liver mass that are observed in rats with the most aggressive gliomas may be accounted for by increased activity of the Cori cycle, with the intermediary metabolism of the glioma-influenced liver being directed toward energy utilization rather than energy storage. In these conditions, liver mitochondria exhibit abnormal biogenesis, together with modifications to water dynamics and ion content.

Improved patient care will result from better understanding of the interactions between brain tumour cells and the immune system, and use of nutritional metabolic therapy to protect tumour-influenced hepatocytes and their mitochondria may improve outcomes.