The study – published in The Journal of Biological Chemistry - tested how overeating affected the ability of insulin in the brain (hypothalamic insulin) to regulate how fat breaks down – finding that high intakes of food leads to blockages in the action on brain insulin, which in turn cause an increase in fat cell metabolism.
Led by Dr Christoph Buettner from Mount Sinai School of Medicine, USA, the researchers note that brain insulin is what suppresses lipolysis, a process during which fats are broken down and fatty acids are released. When this lipolysis is uncontrolled, fatty acid levels rise in the body – which in turn can initiate and worsen obesity and type 2 diabetes.
"We are interested in understanding why people who eat too much eventually develop diabetes,” said Buettner. “Our recent studies suggest that once you overeat, your brain develops insulin resistance.”
“Since brain insulin controls lipolysis in adipose tissue by reducing sympathetic nervous system outflow to adipose tissue, brain insulin resistance causes increased spillage of fatty acids from adipose tissue into the blood stream," he explained.
This uncontrolled release of fatty acids promotes lipotoxicity which is characterised by the inflammation and insulin resistance that leads to and worsens type 2 diabetes, the researchers explain.
Fatty acids also increase glucose production in the liver which raises blood glucose levels, Buettner explained.
"It's a vicious cycle and while we knew that this can begin with overeating, this study shows that it is really the brain that is harmed first which then starts the downward spiral."
Buettner and his team fed rats a high-fat diet – comprised of 10% lard – for three consecutive days. This feeding pattern increased daily caloric intake by up to 50% compared to control rats that were fed a regular low fat diet.
The team then infused a tiny amount of insulin into the brains of both groups of rats – knowing that previous research has shown this to suppress the release of glucose from the liver and fatty acids from fat tissue.
However, the overeating impaired the ability of brain insulin to suppress these actions in normal ways, they said.
Buettner said overconsumption in humans is similarly known to produce comparable effects – which could be explained by the brain insulin resistance mechanism.
"When you overeat, your brain becomes unresponsive to these important clues such as insulin, which puts you on the road to diabetes,” he said. “We believe that what happens in rats also happens in humans."
Source: The Journal of Biological Chemistry
September 2012, Volume 287, Pages 33061-33069, doi: 10.1074/jbc.M111.307348
“Short Term Voluntary Overfeeding Disrupts Brain Insulin Control of Adipose Tissue Lipolysis”
Authors: Thomas Scherer, Claudia Lindtner, Elizabeth Zielinski, James O'Hare, Nika Filatova, Christoph Buettner