Paper published in Cell Metabolism showed that knockout mice had higher cholesterol levels and hardening of the arteries.

Scientists report that insulin resistance in the liver is a key factor in the cause of metabolic syndrome and the associated atherosclerosis. “This study clearly indicates that metabolic syndrome is not merely a collection of abnormalities that should be considered and treated independently, as some experts have advocated,” comments C. Ronald Kahn, M.D., head of the research section on obesity and hormone action, and Sudha Biddinger, M.D., Ph.D., a researcher, both  at Joslin Diabetes Center.

“Rather, it appears that metabolic syndrome is truly a group of closely linked disturbances in glucose and cholesterol metabolism that stem from a defect in insulin signaling in the liver.”

The study sought to understand whether insulin resistance could increase the risk of atherosclerosis.The researchers engineered mice by knocking out insulin receptors in the liver.

From this one site of insulin resistance alone, these mice developed many of the lipid abnormalities associated with metabolic syndrome, according to the research team. Furthermore, when fed a high-fat diet, the mice developed extremely high cholesterol, more than four times the levels found in normal mice fed the same diet, they add. All the knockout mice developed atherosclerosis, while none of the normal mice did, according to the scientists.

The research was performed by investigators at Joslin Diabetes Center, Harvard Medical School, Columbia University, and Massachusetts Institute of Technology. The study is published in the February issue of Cell Metabolism.

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