Beta Adrenergic Receptors Modulate Resistance to Obesity
By Karla Gale
NEW YORK (Reuters Health) Aug 01 - Beta adrenergic receptor signaling mediates diet-induced thermogenesis, and hence body weight homeostasis, investigators report in the August 2nd issue of Science.
According to Dr. Bradford B. Lowell, of Harvard Medical School in Boston, and colleagues, this first direct evidence of the sympathetic nervous system’s involvement in diet-induced thermogenesis was derived through the use of “beta-less” mice, ie, knockouts for the three known beta adrenergic receptors.
Compared with wild-type mice, beta-less mice on a low-fat diet developed mild obesity, even though food intake was similar. The mutant mice exhibited a 16% lower metabolic rate.
When both groups of mice were fed a high-fat diet, the beta-less mice became “enormously obese,” Dr. Lowell told Reuters Health, with incremental weight gain double that predicted from the combined effects of diet and genotype. Comparison of metabolic rates showed a failure of the mutant animals to exhibit diet-induced thermogenesis.
All of the extra weight gained was fat, according to Dr. Lowell. He noted that, after eating the same number of calories, the normal mice gained an average of 6 grams compared with 27 grams in the altered mice.
The brown adipose tissue of the knockout mice exhibited features of normal brown and white adipose tissue, the investigators found. It was larger and paler than in normal mice, and levels of the thermogenic molecule, uncoupling protein-1, were decreased.
As Dr. Lowell noted, the beta adrenergic receptors throughout the body were switched off, so it remains unknown if other tissues are involved in 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, he speculated.
Dr. Abdul G. Dulloo, of the University of Fribourg in Switzerland, notes in an accompanying editorial that diet-induced thermogenesis probably developed as an evolutionary mechanism allowing organisms to overeat large amounts of poor-quality food to obtain essential nutrients without increasing fat deposition.
He suggests that “short-term overfeeding on low-protein diets could provide a very sensitive method for discriminating between those who are metabolically predisposed to leanness or to fatness.”