20 May 2013, BioSpectrum Bureau , BioSpectrum
Singapore: Researchers at Brown University, US, have discovered a molecular chain of events in the brains of obese rats that undermined their ability to suppress appetite and to increase calorie burning. The scientists also found that they could intervene to break that cycle by fixing the core protein-processing problem. The study has been published in the Journal of Biological Chemistry.
Before the study, scientists knew one mechanism in which obesity perpetuated itself and was causing resistance to leptin, a hormone that signals the brain about the status of fat in the body. However, senior author of the study, Dr Eduardo A Nillni, professor of medicine at Brown University and a researcher at Rhode Island Hospital, observed that obese rats had a dearth of another key hormone, called alpha-MSH, after having meals as compared to rats of normal weight.
Alpha-MSH has two jobs in parts of the hypothalamus region of the brain. One is to suppress the activity of food-seeking brain cells. The second is to signal other brain cells to produce the hormone TRH, which prompts the thyroid gland to spur calorie burning activity in the body. In the obese rats alpha-MSH was low, despite an abundance of leptin and despite normal levels of gene expression both for its biochemical precursor protein called pro-opiomelanocortin (POMC) and for a key enzyme called PC2 that processes POMC in brain cells. There had to be more to the story than just leptin, and it wasn't a problem with expressing the needed genes.
Dr Nillni and his co-authors, including lead authors Dr Isin Cakir and Dr Nicole Cyr, conducted the new study to find out where the alpha-MSH deficit was coming from. Dr Nillni said that he suspected that the problem might lie in the brain cells' mechanism for processing the POMC protein to make alpha-MSH.
Dr Nillni said that, "In our study we showed that what actually prevents the production of more alpha-MSH peptide is that ER stress was decreasing the biosynthesis of POMC by affecting one key enzyme that is essential for the formation of alpha-MSH. This is so novel. Nobody ever looked at that."