Researchers uncover potential way to protect against diet-induced obesity and inflammation

Researchers in Spain, funded by the UK charity Worldwide Cancer Research, have discovered a new drug target that could help protect against diet-induced obesity and its related health issues. The research, led by Professors Mercedes Fernandez and Raul Mendez, found that a protein called CPEB4 was present in the fatty tissue of obese patients, and that blocking it in mice protected them from weight gain and associated inflammation, despite a high fat diet, and could therefore have major implications for obesity related diseases such as cancer.

Almost 40% of all adults globally are overweight or obese, and most people now live within countries where being overweight or obese kills more people than being underweight. Obesity is well understood as one of the leading risk factors for cancer development, second only to smoking. In fact, it is estimated that up to half a million cancer cases per year around the world may be caused by obesity.

Very few therapeutic interventions are currently available that effectively treat obesity and lower a person’s associated risk of developing cancer. Therefore, better understanding of how obesity leads to further detrimental health effects is urgently needed.

New research, published in the journal Molecular Metabolism, has revealed a potential new therapeutic target, a protein called CPEB4, that plays a key role in how fatty tissue expands in diet-induced obesity.

Professor Mercedes Fernandez at the Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS) and Institute for Research in Biomedicine (IRB Barcelona), and senior author of the paper explained: “Our work has uncovered a whole new chain of events within the fat cells of our bodies that contributes to obesity, and a specific protein within that process, CPEB4, that has great potential as a target for treating obesity. We found that blocking CPEB4 expression in mice that were on a high fat diet protected them against weight gain, inflammation, and it helped to return the microbiome to a healthier state.

Professor Raul Mendez at the Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS) and Institute for Research in Biomedicine (IRB Barcelona), and senior author of the paper added: “This is particularly interesting as CPEB4 is involved in gene translation, a process which has not been implicated in diet-induced obesity before. Therefore, our findings may highlight an entirely new area of research to explore and create new opportunities to develop better treatments for diet-induced obesity.”

CPEB4 is an RNA-binding protein. Its function in a cell is to read instructions from messenger RNA (mRNA) and produce the proteins and amino acids that those instructions call for. In this study, the researchers found a clear relationship between CPEB4 and increased bodyfat: CPEB4 was found in high amounts in obese patients, but mice that were on a high fat diet and had CPEB4 function blocked put on significantly less bodyfat than control mice. Without CPEB4, fat cells continued to behave like those in healthy weight mice, and not like those seen in obesity.

These findings could have major implications for cancer as obesity and overweight increase the risk of a wide range of cancers. The researchers are now looking at which therapeutic approaches could be used to target CPEB4 in a clinical setting. Obesity is a major risk factor for liver cancer in particular, and so the researchers will also apply their findings to liver cancer as well as cachexia (‘wasting disease’) which accounts for one third of cancer deaths.

Dr Helen Rippon, Chief Executive at Worldwide Cancer Research said: “This exciting discovery provides the foundation for a potential way to tackle the growing global obesity problem and opens the door for researchers to make a start on new cancer cures for the future. Obesity is well-understood as a major risk factor for cancer, and these interesting results can now be taken forward into new projects that explore their potential for reducing obesity and therefore reduce a person’s chance of developing cancer in the first place.

“Rates of obesity are continuing to rise around the world, and without effective interventions many are at considerable risk of developing cancer. In fact, cancer is predicted to become the leading cause of death globally by 2030. Thanks to the hard work of researchers like Professors Fernandez and Mendez, we can have hope for new cancer cures, and new ways to prevent cancer, in the future.”

For more information about Worldwide Cancer Research, please visit: https://www.worldwidecancerresearch.org/.