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A healthy internal clock keeps weight off

Staying up past bedtime, skipping meals, and snacking constantly all add up to weight gain, fatty livers, and high cholesterol levels for an unlucky group of mice whose internal biological clocks are genetically disrupted.

Researchers at Northwestern University and the Howard Hughes Medical Institute have identified wide-ranging molecular and behavioral changes in mice that have a faulty circadian system. In people, similar changes in body fat and metabolic activity are known as metabolic syndrome, which can lead to cardiovascular disease and type 2 diabetes.

The research team, which included co-author Joseph S. Takahashi, a Howard Hughes Medical Institute investigator at Northwestern University, published its report on April 21, 2005, in Science Express, which provides rapid electronic publication of select articles from the journal Science. The study suggests a surprising new angle for understanding and eventually preventing and treating obesity and related disorders in people.

"Timing is critical to keep the metabolic symphony in tune," said corresponding author Joseph Bass, assistant professor of medicine and neurobiology at Northwestern University and head of the endocrinology and metabolism division at Evanston Northwestern Healthcare. Quoting Duke Ellington, Bass added, "It don't mean a thing if it ain't got that swing."

The mice have defective Clock genes that control daily rhythms in the brain and throughout the body, including sleeping and eating. The gene was discovered eight years ago by Takahashi's laboratory. Since then, Takahashi and other researchers have shown that the Clock gene and a half-dozen other proteins run 24-hour oscillating clocks in most cells in the body and in a specific part of the brain that controls appetite and wakefulness. About 3-10 percent of the genes in any given tissue turn on and off in circadian rhythm.

The project started when circadian rhythm expert F
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
21-Apr-2005


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