A new study suggests that the brain of an obese rat hinders the production of a hormone that curbs appetite and instigates calorie burning. The cause can be traced down in a breakdown in the protein-processing mechanism of the cells. In the lab, the researchers prove that the breakdown can be repaired with the use of drugs.
There is a complicated set of neurochemical processes, newly ragged, proves that obesity that obesity can nourish itself, which impedes hormones that affects appetite or increase the burn rate for calories. David Orenstein from Brown University noted how no one has ever looked at the brain cells processing the proteins, which lets obesity go even further. But in a discovery that might prove something in the future, the researchers at Brown University and Lifespan also discovered that they can do something to break that cycle by fixing the core protein-processing problem.
Prior to the study, scientists knew that there is a mechanism, wherein obesity completes itself was by causing resistance to leptin, a hormone signaling the brain in regards with the status of fat in the body. But years ago senior author Eduardo A. Nillni, professor of medicine at Brown University and a researcher at Rhode Island Hospital, discovered that right after rats had eaten something they lack another key hormone — alpha-MSH — compared to rats of normal weight.
Alpha-MSH has two jobs in parts of the hypothalamus region of the brain. The first one is for suppressing the activity of food-seeking brain cells. The second is for signaling other brain cells in producing the hormone TRH, prompting the thyroid gland to spur calorie burning activity in the body.
In the obese rats, alpha-MSH were low, in spite that there is enough supply of leptin and regardless of normal levels of gene expression both for its biochemical precursor protein called pro-opiomelanocortin(POMC) and for a key enzyme known as PC2, processing POMC in brain cells. Scientists knew that there is more to the story than just leptin, and they were able to prove the theory.
Nillni and his co-authors conducted the new study to discover where does the alpha-MSH deficit was coming from. Nillni believe that the problem is somewhere in the brain cells’ mechanism for processing the POMC protein to make alpha-MSH.
Problems that the scientists encountered
For the study, they provided some rats a high-calorie diet while the remaining rats were given with normal diet for 12 weeks. After 12, weeks, researchers noticed that the overfed rats acquired a condition of “diet-induced obesity.” The team decided to conduct some study about the hormone levels and brain cell physiology of the rats.
What they found is that there a key “machine” in the brain cells’ of an obese rat known as endoplasmic reticulum (ER), which is responsible for protein production becomes stressed and overwhelmed. The overloaded ER affects the handling of PC2, perhaps removing it since it can’t be folded up accurately. They found that the PC2 levels in obese rats were 53 percent lower than in normal rats. Alpha-MSH peptides were more than half as plentiful in obese rats as they were in healthy rats.
Scientists now know that a stressed ER cannot handle PC2, which leaves POMC unfolded, which hinders the production of alpha-MSH. They added that the finding needed further experiments before it can be use on people.
The team had proven the study in several ways: In obese rats they measured raised levels of known markers of ER stress. They also introduced induced ER stress in cells through the use of drugs and saw that both PC2 and Alpha-MSH levels dropped.
They need to know if fixing ER stress would enhance the production of alpha-MSH. To do this, the rats were provided with a chemical called TUDCA for two days. TUDCA lessens the stress cause by ER. If ER stress has something to do with alpha-MSH production problems, the researchers would see alpha-MSH recover in obese rats treated with TUDCA. The healthy rats didn’t show an increased production of alpha-MSH, but the obese rats showed an elevated production of alpha-MSH.
They did another experiment and this time it is on the benchtop, in which they took mouse neurons that produced PC2 and POMC and pretreated some of the rats with a similar chemical called PBA highly known for preventing ER stress. Other rats had been left untreated. After that, they tried to recreate ER stress in all the cells. Under that ER stress, those that got treated with PBA emitted about twice as much PC2 as those that had not.
Nillni warned the public that though the study was a success, it doesn’t mean that it is applicable for human. Further study needed before it could be tested on human beings.