Study questions efficacy of weight loss drugs

The scientists based at Oregon Health & Science University have highlighted the complexities of the body’s weight regulation system using rodent models of obesity showing the multifarious factors that can lead to fatness; a problem which is unlikely to be overcome by the simple introduction of cortisol containing medication.

To conduct the research, scientists studied specially bred mice lacking the proopiomelanocortin (POMC) gene. Previous research has shown that mutations to the POMC gene in humans and mice cause obesity, but simultaneously decrease glucocorticoid levels. Because it was unknown whether the primary abnormality occurs in the brain or peripheral tissues, scientists attempted to repair the problem and counteract the obesity by manipulating POMC and glucocorticoid levels.

The scientists did this using two methods. One method was to genetically restore POMC selectively in the pituitary, a gland at the base of the brain that regulates the secretion of cortisol from the adrenal glands, but not in the central portions of the brain. The second method was to directly replace glucocorticoids in POMC-lacking mice through their drinking water.

“In both cases, the mice lacking POMC in the brain did not show improvement in their metabolic state. The treatments actually led to an acceleration in weight gain and development of diabetes,” said Dr Malcolm Low a senior scientist and associate director in the OHSU Center for the Study of Weight Regulation and Associated Disorders.

Low continued: “Importantly, the identical treatments had no discernable effect in control mice with normal POMC levels in the brain. This research demonstrates the important function of the POMC gene in the central nervous system, independent of the pituitary and adrenal glands. It also demonstrates that cortisol alone is not the major culprit in weight gain. Glucocorticoids are merely part of a chain of hormonal and neuronal signals associated with obesity.”