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Weight Loss Surgery May Beat Diet at Inhibiting Cancer

Weight loss surgery was more effective than a low-fat diet at reversing the cancer-promoting effects of chronic obesity in mice, report UNC Lineberger Comprehensive Cancer Center researchers.

"Our basic finding was that surgical weight loss in obese mice was able to inhibit mammary tumor growth in a mouse model of basallike breast cancer, while weight loss induced by a low-fat, low-calorie diet was not," says Emily Rossi, PhD, the paper's first author and a predoctoral trainee with the UNC Lineberger Cancer Control and Education Program.

Rossi and her colleagues in the lab of Stephen Hursting, PhD, MPH, a UNC Lineberger member and a professor of nutrition in the UNC Gillings School of Global Public Health and the UNC Nutrition Research Institute, are leading research to understand and potentially break the link between obesity and cancer.

"Data from human studies has suggested that there is something mechanistically different about bariatric surgery, relative to diet-induced weight loss, that makes the surgery more effective at preventing or controlling breast cancer," Hursting says. "Now that we have (for the first time) replicated this surgery vs diet effect in an experimental model of breast cancer, we have the opportunity to determine the molecular and metabolic factors that are responsible for the protective effects of the surgery."

Obesity is a significant risk factor for several types of breast cancer, including basallike breast cancer subtype. Rossi, Hursting, and their colleagues have shown in previous research that obesity reversal through diet may not be enough to reverse the effects of chronic obesity on molecular drivers of cancer, including epigenetics and inflammation.

In the most recent preclinical study, mice were either fed a low-fat diet or an obesity-promoting high-fat diet for 15 weeks. Obese mice were then randomized to a weight loss surgical procedure called a sleeve gastrectomy, in which the surgeon removes a large portion of the stomach, or to lose the same amount of weight through a low-fat diet.

Rossi and her colleagues found that tumor growth in obese mice that had the weight loss surgery was statistically equivalent to mice that had maintained a normal weight, but obese mice that lost weight through a low-fat diet had less anticancer benefit. Tumor growth in the mice that lost weight by diet mirrored the tumor growth seen in obese mice.

Surgical weight loss was also linked to lower levels of certain molecular drivers of cancer. Mice that went through surgical weight loss had lower levels of insulin and inflammatory proteins, suggesting that the surgery reduced obesity-linked increases in insulin, inflammation and breast cancer growth.

"One consequence of the obesity epidemic in the United States and many other countries is increasing rates of obesity-related cancer," Hursting says. "However, we are not going to solve this growing problem through bariatric surgery, which, despite being effective, is too expensive and too difficult to be done on everyone who is obese. Our goal is to understand what the surgery is doing metabolically to slow tumors, and replicate those protective effects through combinations of diet, exercise, and possibly drugs that target some of the same pathways as the bariatric surgery."

— Source: University of North Carolina Health Care System

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