Patients with cancer often complain about sleep problems and metabolic disturbances.
This is associated with reduced quality of life for patients with such problems. However, until recently the molecular basis for this phenomenon was not known.
Scientists from Ohio State University in the United States have deciphered mechanisms that link cancer to metabolic and sleep disturbances. Using a mouse model of breast cancer, the authors have shown how cancer impacts hormones, metabolism, and the nervous system to cause physiological problems.
Their results were published in Cell Metabolism.
Cancer activates inflammatory responses
As cancer grows, it activates a strong inflammatory response in the body. Since cancer-driven inflammation has been previously shown to cause metabolic problems and sleep disruptions, the authors measured different genes and cells that are typically associated with inflammation in various mouse organs.
To achieve this, investigators use artificial methods to inject cancer cells into mice and then harvest different organs from tumor-bearing mice.
To assess how inflammation affects the sleep-wake cycle in mice, the scientists evaluated how these genes are altered during different hours of the day or night within the brain and the liver of tumor-bearing mice. Since inflammation is known to disrupt liver metabolism, the authors also measured changes in liver metabolic properties throughout the day and night.
Sleep-wake cycles influence how inflammation affects liver metabolism
The inflammation-associated metabolic disturbances in the liver occurred only at specific times of the day and night. This suggested that the sleep-wake cycles greatly influence how cancer-associated inflammation affects liver metabolism.
The authors then looked at different nervous system-associated reasons that may be affected by cancer-associated inflammation.
Specific nerve cells involved in sleeping patterns are affected by tumors
Scientists found that specific classes of nerve cells, called the HO (hypocretin producing) and MCH (melanin-concentrating hormone) neurons are affected by tumors. These nerve cells have been previously shown to be involved in mediating sleeping patterns in mice.
The scientists then looked at the mechanism of how tumors bring about changes in the properties of these neurons.
Physiological experiments showed that the tumors disrupted the production of hormones like leptin and ghrelin which in turn impacted the function of the hypothalamus, a specific region within the brain that houses the HO and MCH neurons. The increased hypocretin activity from these neurons was linked to sleep disruptions.
Targeting HO neurons may help overcome sleep disruptions
What was even more interesting was the finding that blocking the signaling from these neurons allowed the mice to overcome metabolic disruptions and these mice slept better in comparison to controls.
The studies suggested that molecular targeting of HO neurons may one-day aid researchers in developing strategies to overcome metabolic and sleep disruptions in patients and improve the quality of life for patients.
Reference: Borniger, J. C., Walker Ii, W. H., Surbhi, Emmer, K. M., Zhang, N., Zalenski, A. A., . . . DeVries, A. C. (2018). A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer. Cell Metab. doi:10.1016/j.cmet.2018.04.021
