The only known adults in the world who possess a rare genetic mutation that prevents their bodies from producing leptin may open the door to a new way of fighting fat. After injections with leptin -- a human hormone linked to appetite control -- the adults dramatic weight loss suggests that leptin offers significant promise for treating obesity.
Dr. Julio Licinio, professor of medicine at the David Geffen School of Medicine at UCLA, flew three cousins -- two women and one man -- from a tiny village in Turkey to UCLA Medical Center last September for clinical research treatment with leptin. Ranging in age from the late 20s to 40, all of the cousins were severely obese and one was still prepubescent.
"We hypothesized that leptin deficiency may lead to obesity and, in some cases, delay sexual and psychological maturity," explained Licinio, also a professor of psychiatry and biobehavioral sciences at the UCLA Neuropsychiatric Institute. "Although this is a small study, it produced striking results."
Ten months after the study began, the three adults have lost half of their body weight -- more than 150 pounds each. But the leptin therapy resulted in dramatic outcomes beyond their weight loss, including physiological and personality changes.
After receiving leptin injections, the prepubescent adult began experiencing a wide range of physiological changes associated with adolescence and rapidly reached sexual maturity. In addition, UCLA researchers observed neurological growth in all three participants.
"At the end of the study, we measured the subjects brains with MRI and discovered that the organs had expanded a small but significant amount," Licinio said. "While the relevance of this outcome is currently unclear, it poses the first known instance of brain growth in adults."
Earlier research conducted on laboratory animals born without the ability to make leptin showed that they possessed brains 30 percent smaller than their normal counterparts. Until now, however, scientists had never studied the effect of leptin deficiency and replacement in humans.
The cousins dispositions also altered. Within two weeks of leptin therapy, they grew noticeably more assertive and independent.
"The subjects personality changes suggest that there is a relationship between fat and how we feel," Licinio said. "We plan to explore leptins link to mood disorders in the future."
Manufactured in the fat cells, leptin plays three important roles in the human body. First, the hormone signals fullness, controls the appetite and tells the brain to stop eating. Second, it is triggered by puberty and regulates sexual development. And third, it helps the immune system fight off diseases -- a critical weapon in staving off childhood diseases.
According to Licinio, science originally considered leptin a gold mine for weight control. Later, however, researchers discovered that obese people produced too much of the hormone and their bodies simply stopped responding to its appetite cues.
In rare cases, though, some people -- like the adults in Licinios study -- become obese because they manufacture too little leptin. Licinio decided to study the cousins in order to better understand the role that leptin plays in normal human biology.
The only side effect of the leptin replacement therapy was a minor rash at the injection site that lasted briefly in one patient.
Licinio is a member of the Brain Research Institute, director of the UCLA Pharmacogenetics and Pharmacogenomics Research Group, and founding editor-in-chief for The Pharmacogenomics Journal and Molecular Psychiatry.
The UCLA study was funded by the National Institute of Diabetes, Digestive and Kidney Diseases and the National Center for Research Resources. Licinios colleagues at the UCLA Neuropsychiatric Institute included Dr. Ma-Li Wong, Dr. Edythe London, Dr. Sinan Caglayan, and Dr. Bulent Yildez. Licinio also collaborated with Dr. Metin Ozata at the Gulhane School of Medicine in Turkey.
The Thousand Oaks-based pharmaceutical firm Amgen supplied the UCLA researchers with complimentary leptin for the duration of the study and paid $7,500 to Licinio for patient recruitment.
Future UCLA projects will explore the interactions of leptin and other hormones in the elderly, how leptin replacement influences the human endocrine system, and the effect of a single mutation in one of the two genes that encode for human leptin.
Elaine Schmidt | EurekAlert
Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center
Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy