Leptin is a protein hormone that may play a major part in adjusting energy intake and expenditure, including appetite and metabolism. A research from Columbia University Medical Center has claimed that an earlier unidentified leptin-serotonin pathway in the brain, apparently simultaneously encourages appetite and bone mass accrual. The research illuminates as to how leptin which is a familiar appetite-suppressing hormone acts in the brain.
The researchers decided to test this on mice. So when the leptin-serotonin pathway was turned on in mice, the appetite apparently increased. The mice ate more, put on weight, and their bone mass increased. So when the pathway was turned off, the exact opposite supposedly occured. Moreover, leptin was discovered to not perform in the hypothalamus as earlier thought, but in the brain stem acting on serotonin, a hormone in the brain that may act to regulate appetite, mood and anger.
The discovery of this pathway assists in clarifying why obese people are likely to have a drastically lower occurrence of osteoporosis. This is as per the study’s senior author, Gerard Karsenty, M.D., Ph.D., chair of the Department of Genetics & Development at Columbia University’s College of Physician and Surgeons. Though obese people apparently generate high levels of leptin, they are resistant, or indifferent, to its signals, instead they function in a phony condition of leptin shortage, which may increase serotonin and thereby, appetite and bone mass. Dr. Karsenty notes that these existing findings may have more influence on developing a fresh method to supposedly decrease appetite and obesity than averting osteoporosis.
Dr. Karsenty commented, “It will be difficult to turn on the pathway to strengthen bone without increasing appetite at the same time. But this finding shows that it is feasible to alter parts of the leptin-serotonin pathway to decrease appetite without weakening bone.”
The pathway was claimed to be discovered after first observing the dominant effect of leptin on bone mass accrual by Dr. Karsenty and his colleagues. He earlier found that leptin is apparently the most influential inhibitor of bone formation in the body. This new research discloses that high levels of leptin may curb bone formation by closing off the synthesis of serotonin in particular neurons in the brainstem. Dr. Karsenty and his colleagues were shocked to watch that increased serotonin in the brainstem also apparently increased appetite in mice.
Dr. Karsenty commented, “We previously thought that leptin’s modes of action on appetite and bone mass accrual were distinct. But we found instead that they behave more like twins – taking the same pathway through the brainstem. This correlates strikingly with the fact that leptin appears during evolution of bone cells when bone is first formed in the body.”
Dr. Karsenty’s team discovered that the appetite and bone pathways deviate once serotonin is let off. One set of serotonin receptors may turn on appetite, while a second could increase bone mass accrual. The findings may unlock the door for weight loss drugs that apparently have no side effects on bone density.
Dr. Karsenty mentioned, “Theoretically, one can imagine that a drug that blocks only the appetite receptors, but not the bone receptors, could help people lose weight without losing bone mass.”
Dr. Karsenty clarified that the astonishing association between appetite and the skeleton is by observing that the pathway supervises the amount of energy available to maintain bone.
Dr Karsenty remarked, “Our bones are constantly broken down and rebuilt during our lifetimes, and those renovations require an enormous and daily supply of energy.”
Dr. Karsenty, in an earlier research, in November 2008 explained how serotonin released from the gut may be in charge of bone formation. Unlike the brain’s serotonin, an increase in gut serotonin could damage bone formation. Dr. Karsenty’s new research demonstrates that while both origins of serotonin could manipulate bone mass, the brain’s serotonin may control the outcome of serotonin from the gut.
In a few researches, selective serotonin reuptake inhibitors (SSRIs), which may be generally used to treat depression, have supposedly been linked with osteoporosis in a few patients.
SSRIs supposedly improve the action of serotonin, and depending on the person, may result in weakened or strengthened bones. This is as per study co-author J. John Mann, M.D., Ph.D., professor of translational neuroscience (in psychiatry and in radiology) and vice chair for Research in the Department of Psychiatry at Columbia University Medical Center and the New York State Psychiatric Institute.
Dr Mann mentioned, “SSRIs work in the brain and in the gut, but in some people they may work more strongly in the gut. In that case, SSRIs could lead to a decrease in bone growth and osteoporosis.”
These research findings may assist in explaining this phenomenon and could result in possible treatment for this side effect.
This research was published in the September issue of Cell.