"This is not huge obesity," Gozal said, "just 10 percent, a little extra at this stage. This would amount to 15 extra pounds in a human adult." A few of these mice, however, "became morbidly obese at 18 months of age or so," he said. "They died long before their unexposed counterparts."
Offspring from mothers with fragmented sleep revealed health problems in addition to weight gain. They scored poorly on glucose-tolerance tests. They produced normal amounts of insulin but it was less effective, failing to lower glucose levels as expected. Insulin resistance is a hallmark of metabolic syndrome and type 2 diabetes.
They also had disproportionately high amounts of visceral white adipose tissue, the "bad fat," as well as elevated levels of low-density lipoproteins, the bad cholesterol. Plus, their fat cells produced less adiponectin.
Adiponectin is usually a "beneficial hormone," Gozal said. "It can reduce cholesterol, make you more sensitive to insulin, protect your heart." As adiponectin levels in adults go up, body-fat percentage tends to go down. Expression of the adiponectin gene was reduced in the offspring of sleep-fragmented mothers, especially in their visceral fat cells.
A closer look revealed epigenetic changes, such as methylation and histone modification, which shut down selected genes, often in response to environmental stresses.
"We found that the offspring of sleep-deprived mothers had largely inactivated AdipoQ, the adiponectin gene," Gozal said. "Such changes may affect other genes as well; we haven't studied all the potential targets yet. Even so, this is the first example of a perturbation during pregnancy that translates into a genetic risk, in midlife, for the next generation."
|Contact: John Easton|
University of Chicago Medical Center