Science reveals that this type of diet may increase your risk of pancreatic cancer

A recent study linked high-fat diets to increased risk of pancreatic cancer.

Substances believed to boost athletic performance may also activate a receptor that accelerates the development of pancreatic cancer in mice, according to a new study.

The progression of precancerous pancreatic lesions into pancreatic cancer is fueled by a cellular nuclear receptor that is activated by high-fat diets and synthetic compounds found in unregulated athletic performance enhancers, according to a study from the Rogel Cancer Center of the United States. University of Michigan.

Strategies to prevent and treat pancreatic ductal adenocarcinoma, a particularly deadly type of cancer with increasing incidence, are urgently needed. About 55 to 80 percent of people over the age of 40 are thought to have these low-grade precancerous silent pancreatic lesions, which are the main cause of the majority of cases of pancreatic cancer.

Precancerous pancreatic lesions in mice that are similar to those found in humans contained higher levels of the peroxisome proliferator-activated receptor delta (PPARδ), according to research led by Imad Shureiqi, MD The research was published in the log Nature Communication.

Pancreatic tissue in mice

Microscopic images of pancreatic tissue in mice. The image on the left shows tissue with precancerous lesions fed a standard diet; the right shows the same tissue fed with a standard diet plus synthetic PPARδ added. 1 credit

PPARδ controls the expression of several important genes that affect biological processes, including lipid metabolism and cancer development. Pancreatic cancer grows much faster from precancerous lesions when PPARδ is activated. Prior to transferring his research to the cancer center in 2020, Shureiqi worked at the University of Texas MD Anderson Cancer Center, where he performed the majority of this study, particularly in collaboration with Xiangsheng Zuo, MD, Ph.D. .

“We became interested in studying the effects of PPARδ on pancreatic carcinogenesis because our previous observations showed that PPARδ strongly promotes other gastrointestinal cancers. But there is very little information on the role of PPARδ in the development of pancreatic cancer,” Shureiqi said.

PPARδ activation is correlated with excessive exposure to certain ligands, both natural and synthetic. Certain ligands are naturally present in high-fat diets, which have been linked to an increased risk of pancreatic cancer in humans and animal models. High-fat diets are enriched with fatty acids which are natural PPARδ ligands.

Other synthetic forms of PPARδ ligands, such as cardarine (GW501516), are found in exercise supplements, aimed at improving physical performance and endurance. GW501516 was originally designed by pharmaceutical companies to encourage the body to use more fat and to treat non-cancerous conditions such as obesity and hyperlipemia.

Pharmaceutical development of GW501516 and other similar potent PPARδ agonists for medical use has long been halted due to their potential pro-cancer side effects. Although studies of how PPARδ affects colorectal cancer date back to 1999 and pharmaceutical companies have halted development of synthetic PPARδ ligands, unregulated Internet outlets still sell substances like cardarine. The advertisements are largely aimed at young people, claiming that it will help them build muscle endurance and burn fat.

Shureiqi explains that initially, researchers found that these synthetic ligands reduced fatigue in mice. This news made its way to mainstream media, which dubbed it “exercise in a pill.” “Unfortunately, what the media didn’t address was the dark side of PPARδ. Like muscle cells, synthetic PPARδ ligands also help cancer cells get more energy from fat as a fuel source,” he said.

“It’s shocking to me,” Shureiqi continued. “Animal models repeatedly show the strong relationship between PPARδ and cancer promotion in the case of colorectal cancer and stomach cancer. Now we get more information on how it affects pancreatic cancer.

Critical factors that promote progression from silent pancreatic precancerous lesions to pancreatic cancer remain poorly defined, especially those that are easy to target. Although most of these precancerous lesions do not turn into cancer, understanding how they evolve is still critical to finding interventions to combat the rising rate of pancreatic cancer. The results of this study indicate that people who have silent precancerous lesions, even low-grade ones, may increase their risk of developing pancreatic cancer by consuming natural PPARδ activators, such as in high-fat, or synthetic diets, like cardarine.

The future development of effective agents to block PPARδ activation could provide a new approach to prevent the progression of precancerous lesions to pancreatic cancer. Limiting exposure to high-fat diets could also be considered for people with a high prevalence of precancerous pancreatic lesions. But for now, the widespread sales and use of these synthetic, athletic-boosting PPARδ-activating substances are the most pressing cause for concern.

“This new information should alert individuals to the serious potential health risks associated with the use of synthetic PPARδ agonists,” Shureiqi said. “We are trying to get the message across that using these substances is not a good idea. It might improve muscle endurance, but it also improves the cancer’s ability to use energy and grow.

Reference: “Rapid acceleration of KRAS mutant pancreatic carcinogenesis via tumor immune microenvironment remodeling by PPARδ” by Yi Liu, Yasunori Deguchi, Daoyan Wei, Fuyao Liu, Micheline J. Moussalli, Eriko Deguchi, Donghui Li, Huamin Wang, Lovie Ann Valentin, Jennifer K. Colby, Jing Wang, Xiaofeng Zheng, Haoqiang Ying, Mihai Gagea, Baoan Ji, Jiaqi Shi, James C. Yao, Xiangsheng Zuo, and Imad Shureiqi, May 13, 2022, Nature Communications.
DOI: 10.1038/s41467-022-30392-7

The study was funded by the NIH/National Cancer Institute, Cancer Prevention and Research Institute of Texas, DDC Seed Fund, Cancer Center Support, and CPRIT Core Facility Support.

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