C. Ronald Kahn, M.D., senior author on the Cell Metabolism paper
The brain contains more cholesterol than any other organ in the body, produces its own cholesterol and won’t function normally if it doesn’t churn out enough. Defects in cholesterol metabolism have been linked with Alzheimer’s disease and other neurodegenerative conditions. Now researchers at Joslin have discovered that diabetes can affect how much cholesterol the brain can make.
Scientists in the laboratory of C. Ronald Kahn, M.D., head of Joslin’s Integrative Physiology and Metabolism research section, found that brain cholesterol synthesis, the only source of cholesterol for the brain, drops in several mouse models of diabetes. Their work was reported online in the journal Cell Metabolism on November 30.
“Since cholesterol is required by neurons to form synapses (connections) with other cells, this decrease in cholesterol could affect how nerves function for appetite regulation, behavior, memory and even pain and motor activity,” says Dr. Kahn, who is also Mary K. Iacocca Professor of Medicine at Harvard Medical School. “Thus, this has broad implications for people with diabetes.”
“It is well known that insulin and diabetes play an important role in regulating cholesterol synthesis in the liver, where most of the cholesterol circulating in blood comes from,” Dr. Kahn adds. “But nobody had ever suspected that insulin and diabetes would play an important role in cholesterol synthesis in the brain.”
Other investigations have gathered strong evidence that people with diabetes may display varying types of alterations in brain function or ways of responding to stress, he points out. In addition to its potential role in Alzheimer’s disease and other forms of neurological dysfunction, the newly discovered mechanism may play a role in diabetic neuropathy, which remains a large challenge for therapy. Additionally, the research shows a connection between the decrease in brain cholesterol synthesis and appetite, and raises a question about potential interactions between anti-cholesterol drugs and diabetes. The National Institutes of Health and the Iacocca Foundation were lead funders.
This important discovery came from Joslin basic research efforts.
