2024-03-19 06:55:00
Possible cause found Why cancer patients lose so much weight
March 19, 2024, 7:55 a.m
Patients with advanced cancer often appear severely emaciated. Weight loss not only affects quality of life and treatment success, but is also responsible for 20 percent of cancer deaths. Researchers may have discovered the cause.
A Chinese research team has identified a possible cause for the significant weight loss associated with advanced cancer. Elevated lactate levels might be the reason, reports the group led by Xinli Hu and Rui-Ping Xiao from Peking University in the journal “Nature Metabolism”. It is possible that this finding might offer starting points for therapy in the future.
So-called cachexia involves the loss of body fat and muscle mass and affects around 50 to 80 percent of cancer patients. The syndrome is associated with a deterioration in quality of life and poorer tolerability of cancer treatments. Cachexia is responsible for 20 percent of cancer deaths, explains the research team. How and for what reasons it arises in detail and how it might be treated is still unclear.
According to the authors, it is known, among other things, that cytokines produced by cancer cells such as tumor necrosis factor (TNF) and interleukin (IL)-6 stimulate fat and muscle remodeling. However, clinical studies indicated that targeted treatment of inflammatory cytokines is not sufficient to cure cancer cachexia. So far, the syndrome can only be made to disappear if the tumor can be controlled or cured.
Increased lactate levels trigger fat loss
The research team now analyzed metabolic values in the blood of lung cancer patients and mice with cancer-related cachexia and found increased lactate levels depending on the degree of body weight lost. In mice with human cancer cells, the researchers then found that increased lactate levels can trigger extensive conversion of fat tissue, including fat loss, via the GPR81 receptor in white adipose tissue.
Lactate binds to this receptor and activates signals within the cells, as a result of which metabolic activity in fatty tissue is increased, according to the study. This in turn results in the loss of fat and muscle mass and ultimately body weight. In tumor-free mice, cachexia can be triggered solely with a lactate infusion.
The experiments on mice are convincing and the publication is exciting, explained Marina Kreutz from the University Hospital Regensburg, who was not involved in the study herself. “Especially in the last few years, many studies have shown that lactate levels in the tumor of tumor patients correlate with a poor prognosis.” This is due, among other things, to the suppression of the immune system.
Cancer alters glucose metabolism
The extent to which the new results can be completely transferred to humans remains to be seen, says Kreutz. Tumor cachexia often occurs in the final stages of a tumor disease, especially when the tumor burden is high – and the lactate levels in the blood also depend very much on the tumor burden. “The extent to which this is a correlation or actually a causal connection must be clarified in further studies with different tumors and larger numbers of patients.”
Lactate can be produced to an increased extent in cancer; the cause is the so-called Warburg effect: In many cancer cells there is a change in the glucose metabolism. The cells obtain their energy mainly through so-called aerobic glycolysis with subsequent excretion of lactate – this causes lactate levels in the tumor tissue and blood to rise.
The research team concludes from its results that switching off the lactate receptor might possibly be a therapeutic strategy for the treatment of cancer cachexia. In addition, inhibition of the GPR81 receptor also limits tumor growth in mice – the stimulation of GPR81 by lactate apparently plays a role in tumor growth. The researchers suspect that blocking GPR81 might have a double therapeutic benefit: in the treatment of cachexia as well as once morest cancer itself.
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