PROTEIN REGULATES BURNING OF BODY FAT

Muscle movements generate body heat. However, body heat can also be generated in another way: body fat contains a small number of brown adipose cells -- special fat cells that can generate heat without muscle activity. They do this using a protein known as UCP1 that enables babies or hibernating animals to keep warm without shivering. A research team at the University of Veterinary Medicine (Vetmeduni Vienna) has found that a specific chemical compound, an aldehyde, can activate UCP1 under certain conditions, and that could also trigger fat burning. The data were published in the journal PLoS One

The uncoupling Protein 1 (UCP1) is found exclusively in brown adipose tissue. Until some years ago it was thought that only babies and hibernating animals had brown adipose tissue, but since then it also has been found in adults, so UCP1 could be useful in the fight against obesity. "If we can find out how to regulate this protein, we might also find a way to trigger fat burning in the body," explains biophysicist Elena Pohl from the Unit of Physiology and Biophysics at the Vetmeduni Vienna.

UCP1 burns energy

UCP1 is located in the membrane of mitochondria, the power plants that fuel every single cell in the body. Cells that require a lot of energy, such as muscle cells, contain many mitochondria. But brown adipose tissue contains even more mitochondria than muscle tissue. In fact, it is the mitochondria that are responsible for the brown colour of this form of adipose tissue. Regular adipose tissue, which is the majority, is white. UCP1 in mitochondria uses the cell's energy to produce heat. If UCP1 is 'turned off' in mice, the animals will freeze. Hibernating animals would not survive the winter if they did not have this protein.

Researchers aim to regulate UCP1

Elena Pohl and her research group are trying to find a way to regulate UCP1. In a project funded by the FWF, they have tested different substances reported to activate UCP1, under them also reactive aldehyde 4-hydroxy-2-nonenal (HNE).Using an artificial cell membrane containing UCP1, the researchers were able to detect the activity of the protein by measuring the electrical conductivity on the membrane. The researchers dripped HNE onto the membrane and found that UCP1 can be activated by HNE only if combined with fatty acids. "In this model, all the 'players' are known so we could determine clearly whether the substance influences the protein directly or not. The discovery helps to improve our understanding of the mechanisms that regulate UCP1 and may even lead us to a way to burn body fat," explains co-author Olga Jovanovic.

Reducing free radicals

Free radicals play an important role in many biological processes, but they also cause cellular damage and play a crucial role in the pathogenesis of various diseases such as cancer, atherosclerosis and Alzheimer's disease. The research team has also shown that HNE, combined with fatty acids, also has the potential to minimize these damaging free radicals by reducing the membrane potential. "We want to elucidate the molecular mechanisms of UCP. We are still examining various aldehydes and other UCPs. There are five different UCPs and all their functions are not yet fully understood. We hope that our work will contribute to the development of therapies for various diseases."

Drugs in the battle against obesity

In the 1930s, a substance similar to UCP1 was developed that seemed to promise an easy way of losing weight. The substance was called 2,4-dinitrophenol and, like UCP1, it worked as an uncoupler in the mitochondria of cells. Taken in the right amounts, the drug accelerates the human metabolism by up to 50 percent. However, in some cases it caused serious or even lethal side effects and had to be withdrawn from the market. "If we are able to regulate UCP1 in a controlled way, it might be different story," says Pohl.

WORLD FIRST LUNGS AWAITING TRANSPLANT PRESERVED 11 HOURS OUTSIDE BODY

The multidisciplinary transplant team at University Hospitals Leuven successfully preserved a set of donor lungs for over eleven hours with the help of a machine, the longest period ever reported. The lengthy preservation time was necessary because the patient needed a liver transplant immediately prior to the lung transplant. The patient has since left the hospital and is in good health

The patient, who suffered from chronic lung failure, developed sudden acute liver problems and went into a coma. The only surgical option for a patient with a terminal lung disease and a terminal liver disease is a combined lung and liver transplant.

But such double transplants pose a serious timing problem, says Dr. Dirk Van Raemdonck, who helped perform the surgery: "Normally, the lung transplant is carried out before the liver transplant. A donor lung typically can only be preserved outside the body for a maximum of ten hours. And a lung transplant can only be successful if the liver is still working properly. That is why we needed to transplant the liver before the lungs for this patient. To keep the donor lungs in good shape long enough after removal from the donor and prior to transplantation, our medical team used a new preservation technique."

The lungs were not put on ice as they usually are, but were preserved using a machine (OCS LUNG™) that provided continual flushing and oxygen at room temperature. Dr. Van Raemdonck: "The machine enabled us to keep the lungs outside the body for more than eleven hours with no negative effects, the longest period ever reported -- a world first."

World first

The new technique enables doctors to preserve lungs outside the body longer. The machine also provides an analysis of lung quality and can even improve lung function in anticipation of the transplant. A similar machine already exists for kidneys and results show that older kidneys preserved using that machine functioned better immediately after transplantation than kidneys preserved on ice did.

Currently, however, the new technique is not being reimbursed by insurance providers. The technique is being used only in special cases. Costs for this transplantation were covered entirely by University Hospitals Leuven and the maker of the machine.