November 20, 2006

Fat Cells and Cancer Risk

Picture of mouse fat cells Fat tissue from a mouse. averio Cinti and Andrew Greenberg, courtesy of the U.S. Department of Agriculture's Agricultural Research Service

Obesity has been linked with several types of cancer — including those of the colon, breast, endometrium (the lining of the uterus), kidney and esophagus — but why there’s a link hasn’t been clear. A new study in mice brings researchers one step closer to understanding how excess fat might raise the risk of cancer.

A team led by Dr. Allan H. Conney at Rutgers University noticed an interesting phenomenon when they were experimenting with teas and ultraviolet B light (UVB), the part of sunlight that damages DNA, leading to most skin cancers. Green and black tea both provided some protection for mice against UVB-induced skin cancer, but decaffeinated teas didn’t. Caffeine is known to stimulate the breakdown of fat, and the number of tumors was associated with how much tissue fat the mice had. But the researchers also noticed that the caffeine caused the mice to move around more. They thought that the increased activity may have contributed to the animals’ decreased tissue fat. In subsequent experiments, letting mice exercise on a running wheel increased their food intake but decreased their tissue fat. Their body weight wasn’t affected in the end, but the fitter mice wound up with fewer tumors.

Conney and his colleagues, with funding from NIH’s National Cancer Institute, set out to better understand how fat was affecting tumor formation. In the October 31, 2006 issue of Proceedings of the National Academy of Sciences of the United States of America, they explain that mice given a running wheel for two weeks kept their normal body weight but had significantly less fat than control mice kept in cages without a running wheel. The mice with a running wheel ran about two to three miles a day. When they were exposed to UVB light, the fit mice had UVB-damaged skin cells die at a much higher rate than the control mice.

Wondering whether it was the fat itself sending a signal to these skin cells to inhibit their death after UVB exposure, the researchers surgically removed fat from some of the mice and exposed them to UVB two weeks later. They found that the mice who’d had their fat removed surgically also had higher rates of DNA-damaged cell death after exposure to UVB light, just like those who had lower levels of fat after exercising.

These results may help explain why obesity is associated with several cancers. They suggest that fat cells send out signals that keep cells with DNA damage from dying, leaving more damaged cells alive with the ability to one day become cancerous. What these signals might be is a subject for future research.

Using sunscreen and avoiding excessive exposure to sunlight remain the most important ways to avoid skin cancer. A growing body of research, however, is showing that diet and exercise may also play an important role in preventing these and other cancers.

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