Fat Busting Enzyme

Scientists have discovered a mutation in a roundworm that causes them to rapidly burn fat, and they say this could lead to new ways of treating obesity. The study was done at McGill University, and published in Nature. 

The roundworm in question is of the species Caenorhabditis elegans, a small creature only about 1 mm in length. When little food is available, they go into a sort of hibernation state called dauer. During this state they drastically alter their metabolism by shutting down energy consuming processes such as cell division and reproduction. As opposed to normal hibernation though, the worms are able to move around when in this state due to a special storage of lipids. This extra lipid reserve allows the worms to stay in the dauer state for as much as 6 months, which is considerably more than the estimated 2 weeks they would otherwise have managed. 

The newly discovered mutation in some of the ringworms has a considerable impact on their metabolism in dauer, and these worms were shown to die within a week of entering the state. The main reason for this is that they fail to regulate the catabolism of the lipid storage, and thus burn all of it within a few days. This is due to the lack of an enzyme that normally blocks the activity of an important triglyceride lipase, a class proteins that catalyse the hydrolysis of lipids and thus the catabolism of them. The thinking is that the regulating role of this enzyme may translate to humans, and that the faliure of this protein to function properly may lead to increased accumulation of triglycerides and thus lead to obesity. The researchers also believe that it may be possible to develop a drug that inhibits this regulatory enzyme specifically in fatty tissue, and in this way increase the catabolism of triglycerides and decrease patients weight.

It all sounds very similar to what we can achieve with uncoupling proteins. Most of a cells energy (in the form of ATP, or adenosin triphosphate) is generated in the mitochondria by using a generated proton gradient over the inner membrane. When these protons are brought back into the matrix of the mitochondria, they drive an enzyme that generates ATP from ADP (adenosin diphosphate) and a phosphate molecule. Uncoupling proteins are lipophilic proteins that bind to the protons in the intermembrane space and carry them over the inner membrane without driving the ATP-generating enzyme. This means that the energy from proteins, fats and carbohydrates disperses as heat, and is not used to generate energy that the cells can take advantage of. This could rapidly lead to an extreme shortage of energy, a potentially lethal state. One such uncoupling protein is 2,4-Dinitrophenol. Discovered in the 1930s, it is still used by some as a dieting aid and a quick and fast method of loosing body fat. This could cause serious problems though, such as hyperthermia and energy shortage. Not something I would advise taking. 

But, if a drug were developed that worked solely in fatty tissue and could be easily controlled, it could very well be extremely useful in treating obesity. 

Caenorhabditis elegans