Altered hepatic AHR signaling in cancer cachexia impacts liver metabolism

Cancer cachexia is a serious and common complication of cancer disease, characterized by involuntary weight loss, muscle wasting and immune system impairment. Often associated with chronic inflammation and affecting up to 80% of patients with advanced cancers, cachexia compromises response to treatment and results in decreased quality of life and survival of patients.

Laure Bindels and her team (WEL Research Institute – UCLouvain) were interested in the role that the aromatic hydrocarbon receptor AHR could play in cancer cachexia. AHR is known to regulate the expression of genes involved in many metabolic and immune functions. Specifically, AHR is involved in muscle protein degradation and reduction of inflammation, two key mechanisms related to cachexia.

The team demonstrated that AHR activation is profoundly altered in multiple mouse models of cancer cachexia and patient biopsies, independent of food intake. This alteration in the liver contributes to the hepatic inflammatory and metabolic disorders characteristic of cancer cachexia.

The researchers also showed that pharmacological activation of AHR was sufficient to ameliorate liver inflammation and glycaemic disorders in a cachectic mouse model. As there is currently no treatment available, these results may pave the way for future therapeutic approaches to tackle cancer cachexia.

Reference: Dolly et al (2023) J. Cachexia Sarcopenia Muscle, doi: 10.1002/jcsm.13246

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