Jeonga Kim, Ph.D.

A novel therapy developed at the University of Alabama at Birmingham ameliorates obesity and Type 2 diabetes in mice fed a high-fat diet. The therapy acts through sustained release of nitric oxide, a gaseous signaling chemical whose most important function in the body is relaxing the inner muscles of blood vessels.

“Because reduced bioavailability of nitric oxide is the hallmark of cardiometabolic syndrome, supplying exogenous nitric oxide at a sustained level may be an efficient way of treating the cardiometabolic syndrome,” said Jeonga Kim, Ph.D., leader of the UAB study. “The strategy of reducing body weight by the local delivery of nitric oxide may be a novel, efficient and safe way to prevent and treat multiple metabolic diseases.”

This study, published in the journal ACS Applied Materials & Interfaces, used an ingenious self-assembling, nanomatrix gel capable of releasing a burst of nitric oxide in the first 24 hours, followed by sustained nitric oxide release for four weeks. The gel was developed by UAB researchers Ho-Wook Jun, Ph.D., and Brigitta Brott, M.D., and it is licensed through the UAB Harbert Institute for Innovation and Entrepreneurship by their UAB spinoff company, Endomimetics LLC.

The gel was injected subcutaneously into 8-week-old mice every two weeks for 12 weeks. Gel-injected mice and control mice were fed a high-fat diet, known to induce obesity and insulin resistance.

At the end of 12 weeks, the nitric oxide-mice had gained 17 percent less body weight, compared to controls, and that weight difference was due mainly to decreased fat, not lean mass or water content. The researchers saw increased phosphorylation of the enzyme hormone-sensitive lipase and a reduction in the size of fat cells in epididymal white adipose tissue, or eWAT. Increased lipolysis may explain the reduced body weight, Kim says.

The nitric oxide-mice also showed improved glucose tolerance, and decreases in fasting serum insulin and leptin levels.

Kim and colleagues found wide-ranging changes in measures of inflammation and metabolism in the nitric-oxide mice, compared to controls. The expression of four inflammatory genes, including a marker for macrophages, was reduced in eWAT.

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