Thu Aug 1, 2002
By Merritt McKinney
NEW YORK (Reuters Health) - Many scientists have suspected the body tries to prevent weight gain by heating up the calorie-burning furnace when we eat too much, but proving this hunch has been difficult. Now, a new study in mice provides the first proof that this weight-control mechanism, known as diet-induced thermogenesis, does exist.
The research does not prove that the same phenomenon exists in people. But if the findings are confirmed, they could point the way to new targets for anti-obesity drugs, according to the study's senior author, Dr. Bradford B. Lowell, of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts.
When Lowell's team fed a high-fat diet to normal mice and to mice that lacked three receptors thought to be involved in diet-induced thermogenesis, both groups gained weight, but the genetically altered mice nearly doubled in size.
"They got enormously obese," Lowell told Reuters Health in an interview. All of the extra weight gained was fat, according to Lowell. He noted that both groups of mice ate the same number of calories, but the normal mice gained an average of 6 grams compared with 27 grams in the altered mice.
"This entire defect is due to an abnormality in energy expenditure," Lowell said.
The Boston researcher explained that how much we weigh depends on a balance between how many calories we eat and how many we burn. He noted that physical activity burns calories as do the body's normal functions, such as the beating of the heart.
But in certain situations, such as when the body is exposed to cold or takes in too many calories, Lowell said that the body is thought to try to prevent weight gain by changing the rate at which calories are burned. Until now, there has been no proven explanation of how the process of diet-induced thermogenesis occurs.
The body's sympathetic nervous system, which comes into play during stressful situations, is thought to be involved in burning extra calories, so Lowell's team focused on three molecules known as beta-adrenergic receptors that are involved in this part of the nervous system and are believed to initiate the process of diet-induced thermogenesis. They tinkered with the mice's genes to make them lack active beta receptors.
The findings are published in the August 2nd issue of the journal Science.
The study is a "definite demonstration" that diet can have an effect on thermogenesis and that this process involves beta receptors, Lowell said.
According to Lowell, the research raises several questions, including what happens "upstream" of the beta receptors. He noted that the receptors are located in tissues throughout the body, but one of the major questions is how the brain is involved in regulating diet-induced thermogenesis.
If future research uncovers how diet-induced calorie-burning takes place on a molecular level in tissues, it "may reveal new targets for drug therapy" for obesity, Lowell speculated.
Of course, what occurs in mice does not necessarily occur in people, but Lowell said there is a "good chance" that a similar mechanism exists in people. He noted that the same direct evidence for the existence of diet-induced thermogenesis, which has now been confirmed, also exists in people.
The study was funded by the National Institutes of Health and Eli Lilly and Company.
The study is "something of a triumph," according to Dr. Abdul G. Dulloo, of the University of Fribourg in Switzerland. He notes in an accompanying editorial that several attempts to trigger obesity by switching off genes in the sympathetic nervous system have not succeeded.
As to whether defects in the diet-induced thermogenesis that eventually lead to obesity are caused by variations in the sympathetic nervous system "remains to be firmly established in humans," according to Dulloo.
SOURCE: Science 2002;297:843-845.