May 12, 2005

Faulty body clock leads to obesity

By Megan Fellman

Obesity and diabetes in both adults and children are rising at alarming rates and a wide range of culprits — super-sized food portions, lack of exercise due to television, computers, suburban sprawl and loss of gym classes, high-fat and fast foods, sugar-laden drinks and psychological trauma — have been blamed.

Now researchers from Northwestern and Evanston Northwestern Healthcare (ENH) have pinpointed something deep within the brain and other tissues that plays an important role in the struggle to maintain a healthy weight: the body’s 24-hour internal clock. The research team, led by an endocrinologist and a circadian rhythms expert, has shown that a faulty or misaligned body clock, which regulates both sleep and hunger, can wreak havoc on the body and its metabolism, increasing the propensity for obesity and diabetes.

The findings were published online by the journal Science.

“Just as there is a mechanism that makes the heart beat, there is a clock that functions in many different parts of the body to regulate many different systems,” said Joseph Bass, M.D., senior author and assistant professor of medicine and neurobiology and physiology at Northwestern and head of the division of endocrinology and metabolism at ENH.

“We don’t know too much about how clocks control eating and metabolism in normal individuals, but now we have shown that weight gain and abnormalities in metabolism, including diabetes, result if this internal timepiece is malfunctioning. The body clock is clearly controlling the elaborate brain signaling system that regulates appetite.”

“We’ve demonstrated that an animal model with a known circadian disregulation — a mouse with a mutant Clock gene and thus an imprecise body clock — has metabolic problems, at least obesity and signs of the metabolic syndrome,” said circadian rhythm expert Fred W. Turek, lead author on the paper and professor of neurobiology and physiology in the Weinberg College of Arts and Sciences.

“This provides new genetic evidence that physiologic outputs of the biological clock, sleep and appetite are interconnected at the molecular and behavioral levels, yielding implications on the role of internal biological timing in optimizing strategies to reduce and sustain weight loss resulting from both medical and lifestyle modifications.”

The research team also includes Joseph S. Takahashi, Walter and Mary Elizabeth Glass Professor in the Life Sciences and a Howard Hughes Medical Institute investigator at Northwestern, who led the team that cloned the first mammalian circadian gene, Clock, in 1997. This discovery provided the genetic model critical to this study reported in Science.