Team IDs strategic link in obesity-diabetes process

Team IDs strategic link in obesity-diabetes process

Juli Bai, Ph.D. (left) and Feng Liu, Ph.D., in their lab.

Obesity does a lot more than make us hesitant to go to the beach in our swimsuits. Scientists are finding that, far from being innocent or harmless, extra weight fuels inflammation, impairs cell energy and fosters insulin resistance.

All of this can lead to diabetes.

“There are missing gaps in our understanding of this process,” said Feng Liu, Ph.D., professor of pharmacology at The University of Texas Health Science Center, now called UT Health San Antonio™.

Dr. Liu is senior author of new research—published Oct. 30 in Proceedings of the National Academy of Sciences—that at least partially explains how obesity, mitochondrial dysfunction, inflammation and insulin resistance can all be linked.

Insulin is the hormone secreted by the pancreas to control blood glucose. In type 2 diabetes, insulin-producing cells decrease in number and the available insulin isn’t used efficiently (known as insulin resistance). Obesity is well known to be a risk factor causing insulin resistance, yet the underlying mechanisms remain elusive.

Mitochondria are the energy centers in cells. Our bodies need these power plants to operate properly because all organs, especially the brain, require ATP, which is the body’s energy currency.

Obesity impairs mitochondrial function, which leads to the activation of a specific biological pathway in obese mice, the UT Health San Antonio team found. The scientists also noticed that deactivating the pathway reduces inflammation and improves insulin sensitivity, making the body more responsive to insulin.

The pathway, called cGAS-cGAMP-STING, was long known to be involved in the immune system’s response to viruses and bacteria. The pathway is activated by viral and bacterial DNA.

In recent years, scientists also found that the cGAS-cGAMP-STING pathway is activated by mitochondrial DNA. The UT Health San Antonio team hypothesized that obesity might also activate the pathway.

“So we tested this hypothesis in two different mouse models of obesity,” Dr. Liu said. “In both models, this pathway is activated. It showed, for the first time in the obesity-metabolism field, that activation of this pathway may play a role in obesity-induced inflammation and insulin resistance.”

This discovery provides a potential pharmacological target for intervening in the damaging effects of obesity. “This is very exciting, because it shows a mechanism that links obesity, mitochondrial dysfunction, inflammation and insulin resistance,” Dr. Liu said.

Juli Bai, Ph.D., postdoctoral fellow in Dr. Liu’s lab, is first author of the paper. The authors are from the Joe R. & Teresa Lozano Long School of Medicine at UT Health San Antonio.

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