New Obesity drugs: Coming Soon to a Store Near You!
Afraid to go into public because you think those double doors might be a little narrow for you? Are you pretty sure you have feet, even though you haven’t seen them for awhile now? Did you recently find something you think may have been a twinkie at one point in your folds? If you answered yes to any of these questions, then science might be able to help.
Believe it or not weight gain is complex –or at least the biological aspect of it– for example hormones control our appetite and even the uptake of food. In recent years, science has taken on the seemingly insurmountable quest of investigating these physiological functions and finding a medical way to fight the ever growing obesity epidemic.
One way that has attracted scientific interest is to work with a special protein, one that can stimulate different physiological activities such as the production of appetite controlling hormones [to help make you feel full longer] and hormones that control the intestinal uptake of food.
The particular protein we are talking about is found in the cell membranes in intestines, in immune cells and in — of course– fat. This protein is called FFA4. The protein is activated by long-chain free fatty acids released from the food such as omega-3 fatty acids. When this happens, it releases hormones that inhibit appetite and increase sugar uptake from the blood [this part is controlled, of course, by insulin].
“In some people this protein is not activated and they have a much higher risk of becoming obese. This can be explained by the involvement of the protein in hormone secretion and regulation of inflammation and insulin sensitivity”, explains postdoc Bharat Shimpukade from Department of Physics, Chemistry and Pharmacy at University of Southern Denmark.
The goal is to find a molecule that will activate this protein. It sounds like a simple enough task, but there are almost an infinite number of possible molecules that can be synthesized. This means it could take years of experiments in a lab to get the job done.
“We have developed a computer model of FFA4 that can help us to select the correct molecules for synthesis by first testing if they bind in the computer model. This way we can test thousands of molecules in a very short time before going into the laboratory. This will speed up the process of finding the right compounds that can be developed to efficient drugs against obesity or diabetes”, says Bharat Shimpukade. The model has been confirmed and refined by detailed experimental studies.
It just so happens that in 2012, the same team discovered the first selective activator of FFA4, a compound that is now important for studying the functions of the protein.
“It works well at activating the protein. But we cannot administer it as a drug to a patient, because it is not stable enough in the body. We need a more water-soluble molecule with higher stability: It must not be broken down in the body before it has done the job. On the other hand, we don’t want it to stay in the body forever.”
The team has now set out to find the right molecule that will activate the protein in just the right ways and stay in the body for just time needed [too long could lead to problems and too short will be ineffective].Of course to do this, they are using the new model.
So with a little luck, you could be looking at a pill to get rid of those extra pounds. Maybe it’s the easy way out and you should just diet and eat right, maybe there is some biological reason, or maybe it is just our diets. No matter what it is, the obesity epidemic is here and doesn’t seem to be going anywhere any time soon.
Already know your metabolic pathways? You probably want the full study, which you can find —here!
Hudson, B., Shimpukade, B., Milligan, G., & Ulven, T. (2014). The molecular basis of ligand interaction at free fatty acid receptor 4 (FFA4/GPR120) Journal of Biological Chemistry DOI: 10.1074/jbc.M114.561449