One Third of Cancer Patients Killed by a 'fat-burning'

It was just a couple of years ago that the importance of the transformation of white fat into brown fat was understood. Most fat in adult humans is white—white adipose tissue—and we know that its main function, but not its only function, is to store energy (those love handles). Brown fat, however, is burned to produce heat; baby fat and the fat of hibernating animals is like that. In the context of the current obesity epidemic, white fat has been labelled bad fat, while brown fat is the good one.

The discovery that adult humans can turn white/bad fat into brown/good fat via exercise or exposure to low temperatures has opened a new line of attack on obesity, and in fact the active search for pharmacological tools to induce the transformation of fat is well underway.

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The work of Wagner's group in the article in Cell Metabolism does not discuss the advantages or disadvantages of each type of fat, it rather highlights that a process that could be strengthened to fight obesity must be fought against in cancer patients.

As for cachexia, it is a less-studied phenomenon despite that doctors have known for a long time that the treatment is difficult and the prognosis negative. Next to patients with cancer, it also affects patients in advanced phases of many illnesses, including infectious diseases, such as AIDS or tuberculosis, and chronic illnesses, such as multiple sclerosis.

It Is Not 'Self-Cannibalism'

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CAC has until recently been interpreted as a kind of self-cannibalism: the body 'consumes' itself while trying to supply the energy needs of the constantly growing tumour. Today we know that tumours of any size can cause cachexia, including very small ones, and even at very early stages of tumour development, which does not fit with the idea of self-cannibalism. Researchers have observed that the process does not respond either to the body's greater need to generate heat.

These new data, and the often ignored fact that it is the cachexia associated with the tumour—and not the tumour itself—that causes the death of one third of cancer patients, has encouraged the study of this syndrome in recent years. It is now known that this process is tightly associated with inflammation, a hallmark of many cancer types.

This is why in their study Wagner and his group explore the link between inflammation, cachexia and the process of transforming white fat tissue into brown fat tissue. Their results indicate that if the activity of one of the agents that promotes inflammation—cytokine IL-6—is blocked, the fat transformation process is substantially reduced and, as a consequence, the cachexia. The researchers do point out that it is not a cure: IL-6 is just one of several cytokines involved in the process and blocking it is not enough.

A Way To Prevent Cachexia

These novel results suggest that anti-inflammatory drugs could help fight cachexia, but there is a problem: the lack of knowledge about this syndrome is such that for now it is not possible to predict which cancer patient will develop cachexia. Furthermore, anti-inflammatory drugs have often side effects, and therefore these treatments cannot be used to prevent the appearance of cachexia in all cancer patients.

The current study in Cell Metabolism could open up a new way of discovering processes, eg the transformation of fat in the initial stages of cachexia. "It allows one to think of the possibility to identify biomarkers that would help to predict which patients are going to develop cachexia in a way we can treat them preventively", says Petruzzelli.

Source-Eurekalert