Genetic factor controls obesity-induced inflammation

Washington: Scientists have discovered a genetic factor that can regulate obesity-induced inflammation that contributes to chronic health problems.

Researchers at Case Western Reserve University School of Medicine feel if they learn to control levels of the factor in defense cells called macrophages, they would find a new treatment for health-harming obesity.

“We have a shot at a novel treatment for obesity and its complications, such as diabetes, heart disease and cancer,” Mukesh K. Jain, MD, Ellery Sedgwick Jr. Chair, director of the Case Cardiovascular Research Institute, and senior author of the new study, said.

Macrophages contain low levels of KLF4 and are more easily irritated by cytokines, which are cell-signalling proteins, and fatty acids released by fat cells, and they respond by producing a low level of inflammation, Jain explained.

“A low level of inflammation over time is deleterious,” he said.

In people, long-lasting inflammation is connected to diabetes, increased risk of cardiovascular disease, cancer and other chronic illnesses.

In experiments using mouse models, Jain’s team found that when KLF4 was removed from macrophages, they all assumed the inflammatory state.

Furthermore, when the KLF4-deficient mice were fed a high-fat diet for 10 weeks, they gained 15 percent more weight than control animals fed the same diet, and developed severe diabetes as evidenced by glucose tolerance tests.

The researchers are now designing experiments to determine if they can prevent or reverse the shift from anti-inflammatory to inflammatory by increasing KLF4 levels in macrophages as cytokines or fats bombard them.

The findings have been published online in the Journal of Clinical Investigation.


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