DIABETES
July 4, 2014

Obesity, Diabetes and Cancer Linked

The obese suffer from chronic inflammation in fat cells. This not only can bring on diabetes, it may also promote cancer.

According to the Center for Disease Control, the US population is eating itself into an epidemic. Obesity and diabetes are two of the biggest public health challenges of the century and, of the people diagnosed with type II diabetes, about 80 to 90 percent are also obese.

Scientists have long known that obesity is intertwined with diabetes, and now new findings shed light on how the same process in obesity is also linked to cancer.

Cells in obese individuals are constantly in a state of hypoxia, leading to a massive and chronic inflammatory response.

The connection is a protein that appears to play a key role in the development of insulin resistance, one of the hallmarks of type II diabetes, according to researchers from the University of California San Diego. Mice that were genetically engineered to lack this “HIF-1 alpha” protein in their fat cells still developed obesity when fed a high-fat diet, but they did not develop insulin resistance or diabetes as frequently as normal mice, the team found.

“There is clearly a greater chance among the obese human population to develop insulin resistance and diabetes. We still don't know the exact mechanism, but now we know that HIF-1 is very active in the pathogenesis of these diseases from obesity,” Jung-whan Kim, co-lead author on the study, said.

The findings are important because they may illuminate pathways to fight insulin resistance and diabetes. And they are doubly important because of their relationship to cancer.

HIF-1 stands for “hypoxia inducible factor-1.” Hypoxia refers to a condition in which cells are deprived of oxygen. Cells in this condition switch their metabolism, producing molecules that cause damage to the body in the process. The HIF-1 protein is responsible for triggering an inflammatory response aimed at stopping the production of these harmful molecules.

Cells in obese individuals are constantly in a state of hypoxia, leading to massive and chronic inflammation. Rapidly-growing tumor cells also are hypoxic and elevate HIF-1 levels in response. And that connection may offer a connection to cancer and possible treatment.

“Tumor cells grow really fast, but the blood vessels that feed them oxygen cannot grow fast enough, so tumor cells become hypoxic,” Dr. Kim explained. “The tumor cells have to develop some sort of mechanism to survive under hypoxic stress, and that's HIF-1.”

Inhibiting HIF-1 in tumor cells would lead to cell death, and several pharmaceutical companies are already developing HIF-1 inhibitors that might block the protein from functioning. While such drugs may prove useful in treating insulin resistance in obese people, the pharmaceutical industry is more interested in investigating their potential for fighting cancers.

“There is a clear correlation between [obesity and cancer], but it's not clear why obese people have a greater chance of developing certain cancers,” said Dr. Kim. He hopes to study the interaction between breast cancer cells and fat cells in the near future. “If you look at breast cancer, the glands that produce milk are completely surrounded by fat cells.”

The study is published in Cell.

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