Hibernation is one of the many mysteries of modern science. Anatomical and behavioral studies have revealed very little about the inner workings of this amazing ability. Hibernating animals can to lower their body temperature to 2° C and their heart rate to 2 beats per minute, while reducing their intake of oxygen to 1/50 of their waking levels. All of this occurs without consuming food and can last for as long as 6 months. Current progress in biochemistry and genetic research has finally started to enable our knowledge to catch up to our curiosity in this field. Several different factors have been discovered for the process of reducing the metabolic activity of the body and maximizing its efficient use of energy. Interestingly enough, the same genes may be latent in human beings.
While hibernating animals reduce their metabolic rate substantially, they still need to keep their bodies warm. The protein thermogenin has been found to uncouple the electron transport chain from the process of making adenosine triphosphate (ATP). The result is the production of heat, thermogenesis, instead of the ATP energy that would be usable by the body. The electron transport chain is a series of membrane proteins, which, in the processes of metabolizing food or food reserves, produces a very high concentration of hydrogen ions in the inter-membrane space of a mitochondrion. The matrix of the mitochondrion, which has relatively few hydrogen ions, and the intermembrane space are separated by a single lipid bilayer membrane. The result is an imbalance much like that of the waters on either side of a dam. On power producing dams there are generators that are able to convert the energy produced by the movement of the water through the dam into useable electricity. The generator of the mitochondria is called an ATP synthetase. ATP is the basic currency of energy used to drive most of the body’s functions. The generators make ATP by using the energy of the hydrogen ion movement across the membrane to attach a phosphate group to ADP. Thermogenin works by leveling the water on both sides of the dam. It’s as if someone were to poke a hole into the dam so that water could flow to the other side without passing through the generator. In the case of the mitochondrial inner membrane the "hole" is a protein channel from the intermembrane space to the matrix. The energy that would have been converted to ATP is then released as heat. The presence of thermogenin in high quantity produces a darker color in animal adipose tissue, commonly called brown fat.
Slowing Down Metabilism
Recent discoveries regarding hibernation are not limited to understanding the changing of the use of the hydrogen ion gradient in mitochondria. Pyruvate dehydrogenase kinase isozyme 4 (PDK-4) slows the metabolism by inhibiting pyruvate from being converted to acetyl-CoA. Acetyl-CoA would normally enter the tricarboxylic acid cycle (TCA) and eventually lead to oxidative phosphorylation, which produces the supplies to fuel the electron transport chain and the production of ATP. Pyruvate is converted to acetyl-CoA by the enzyme complex pyruvate dehydrogenase. PDK-4 inhibits this enzyme by initiating the phosphorylation of one of the subunits of the enzyme complex. The effects of PDK-4 are currently considered the reason for a 96% drop in pyruvate dehydrogenase activity during hibernation. This inhibition can later be reversed by another enzyme, pyruvate dehydrogenase phosphatase, upon cessation of hibernation.
Shift in Fat Utilization
Pancreatic lipase (PL) is also a contributor to the process of hibernation. Under non-hibernating conditions PL is expressed solely in the pancreas to break triacylglycerols from foodl into glycerol and fatty acids through hydrolysis.
These components can then be used by the body as a source of energy. During hibernation the lipase is produced in other areas of the body, such as the tissues of the heart, wherethis stored energy as fat is needed most. PL is used significantly more during hibernation because it is able to perform at temperatures well below the range of other lipases. Because of the body’s dependence on energy released from fat during hibernation in the cold of winter, it must have a lipase that is viable at low temperatures.
Future Human Applications
Since the basic mechanics of hibernation are now coming to light one cannot help but wonder if the process is possible in humans. Hibernation may help assist in surgeries to reduce or avoid the use of anesthetics, which are extremely dangerous if used for long periods. Hibernation could take the time-limiting factor out of these surgeries. Hibernating animals also show a very low amount of muscular atrophy. A human wouldn’t be able to walk after a few months of lying in bed. By contrast, a ground squirrel can be quickly up and running after 6 months of hibernation. In the future, as we better understand the process, hibernation may also be used for space travel, not just for long term sleep, but also to preserve the muscles of astronauts from atrophy. Some have even considered the application of hibernation principles to the storage of organs for transplantation.
Hibernation occurs in members of almost every type of mammal. Monotremes, marsupials, primates, rodents, bats and many others all hibernate. This information suggests hibernation may be a very early development in mammals. The genes for PL and PDK-4 are also found in humans. Triggering them into initiating hibernation may be a simple process of helping our bodies "remember" the traits of our own ancestors.
