April 30, 1997
New study of the genetic causes of obesity defies traditional thinking about the role of adrenaline
Scientists have long thought that the sympathetic (or autonomic) nervous system determines how the body uses energy from food, deciding whether calories are burned up to keep the body warm, or stored in the form of fat.
However, new studies reported in the May 1 edition of Nature appear to contradict traditional thinking about the sympathetic nervous system’s influence in people who never gain weight no matter how much they eat, versus those who seemingly put on pounds if a piece of cheesecake is merely passed under their nose.
To test whether deficiencies in the sympathetic nervous system may be a cause of obesity, University of Washington researchers Dr. Steven A. Thomas and Dr. Richard D. Palmiter produced mice that cannot make adrenaline (the hormone of the adrenal gland) or noradrenaline (the chemical messenger of the sympathetic nervous system). These two compounds are released in response to stress and regulate many body functions, including the ability to keep warm.
The mice that cannot make adrenaline and noradrenaline are unable to increase heat production, and they cannot defend themselves against heat loss; consequently, they lose heat rapidly in the cold.
“This was expected,” said Palmiter, UW professor of biochemistry and an investigator of the Howard Hughes Medical Institute. “However, many scientists believed that under normal temperatures these mice would become obese because they wouldn’t burn excess calories but instead would deposit them as fat.”
“Instead, we found that at normal temperatures these mice do not become obese, despite the fact they eat more than normal,” said Thomas, a senior fellow in biochemistry and first author of the UW study. “Our research suggests that obesity is not likely to involve defects in the sympathetic nervous system or in the production of adrenaline.”
Noradrenaline normally produces heat by stimulating the production of protein called the uncoupling protein (UCP) in special brown fat cells. In the mice that lacked noradrenaline, this production did not take place.
A second study in the same issue of Nature corroborates the UW findings. Scientists at the Jackson Laboratory in Bar Harbor, Maine, produced mice that cannot make UCP. Like the UW mice, these mice do not become obese and they, too, are more sensitive to the cold.
A previous study by Drs. David E. Cummings and G. Stanley McKnight of the UW School of Medicine’s Department of Pharmacology (published in Nature last year) indicated that chronic activation of the pathway leading to UCP production resulted in lean mice. Thus, there was ample reason to think that the opposite might be true if mice could not increase heat production after eating a meal.
“Both of the current studies, done independently and without each others’ knowledge, produced consistent and unexpected results that are leading us to look in new directions for the genetic causes of obesity in humans,” said Thomas.
The UW research was funded by grants from the Howard Hughes Medical Institute and the National Institutes of Health.
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