Diabetes may clamp down on cholesterol the brain needs

Nov 30, 2010

The brain contains more cholesterol than any other organ in the body, has to produce 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 Diabetes Center 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 on November 30.

"Since cholesterol is required by 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." 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.

"It is well known that 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."

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.

People with diabetes are also known to be more prone to depression, and eating disorders than people without diabetes, and imaging studies have shown that people with diabetes have altered compared to those without.

Additionally, the finding raises a question about potential interactions between anti-cholesterol drugs and diabetes.

In the Joslin study, scientists first examined gene expression in the hypothalamus of a mouse model of insulin-deficient (type 1) diabetes. They found decreased expression for almost all of the genes of cholesterol synthesis, including a gene called SREBP-2, which acts as a master regulator for cholesterol production. Similar findings were present in the cerebral cortex and other regions of the brain in these animals and also found in several other mouse models of diabetes. In the insulin-deficient animals, this phenomenon was associated with decreased cholesterol synthesis. Treatment of the mice with insulin, either by normal injection or injection into the fluid surrounding the brain, reversed the process.

"Our studies showed that these effects occurred in both the neurons and supporting 'glial' cells that help provide some nutrients to the neurons," says Kahn. "Ultimately this affects the amount of cholesterol that can get into the membranes of the neuron, which form the synapses and the synaptic vesicles—the small structures that contain neurotransmitters."

Additionally, the Joslin work showed a connection between the decrease in brain cholesterol synthesis and appetite. When the scientists took normal mice and temporarily reduced creation in the hypothalamus with a technique known as RNA interference, the animals started eating more and gained significant weight. Previous studies by other labs have demonstrated that diabetes may affect brain hormones involved in appetite regulation.

Explore further: Australian treatment could save wounded soldiers

Provided by Joslin Diabetes Center

5 /5 (1 vote)
add to favorites email to friend print save as pdf

Related Stories

Prions link cholesterol to neurodegeneration

Feb 12, 2008

Prion infection of neurons increases the free cholesterol content in cell membranes. A new study published in the online open access journal BMC Biology suggests that disturbances in membrane cholesterol may be the mechan ...

High insulin levels impair intestinal metabolic function

Apr 24, 2007

Nutritional scientists at the University of Alberta are the first to establish a connection between high insulin levels and dysfunction of intestinal lipid metabolism in an animal model. They believe this finding supports ...

How drug that blocks cholesterol absorption from the diet works

Jun 03, 2008

A new study in the June issue of Cell Metabolism, a Cell Press publication, sheds light on the action of the drug ezetimibe (trade name Zetia), which is used to treat high cholesterol. Ezetimibe is unique among cholesterol-lowering drugs ...

Recommended for you

A hybrid vehicle that delivers DNA

18 hours ago

A new hybrid vehicle is under development. Its performance isn't measured by the distance it travels, but rather the delivery of its cargo: vaccines that contain genetically engineered DNA to fight HIV, cancer, ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

vtel57
not rated yet Dec 01, 2010
The human body is a very complicated machine. It's going to be a long while before we understand its inner workings 100%. Until then, we test and experiment. Sometimes, the scientists are right; other times not.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.