Obesity is a complex disease involving an excessive amount of body fat. This may pave the way for other catastrophic conditions like diabetes, atherosclerosis, high blood pressure, and even cancers. There a lot of people in the world struggling to reduce their fat once it is laid well in the body tissues. On average, it affects 40 percent of adults in the United States and 13 percent of the global population. There are many anti-obesity drugs used today, but none of them are completely effective. Researchers are trying to combat the condition with the help of molecules that stops fat formation.
Webstar Santos, a Professor of Chemistry in the College of Virginia, has identified a molecule BAM 15 that can help to reduce the body fat mass of mice without affecting food intake and muscle mass or increased body temperature. The molecule is an uncoupler in oxidative phosphorylation, and it is highly potential to treat the patients when compared to other uncouplers.
Mechanism of BAM 15 in the body
Mitochondria, the powerhouse of the cell since it generates ATP that is helpful in all biological processes in our body. The food that we are eating is digested by several enzymes to break into a small molecule, and they then undergo several pathways such as glycolysis, TCA cycle, and electron transport chain to yield ATP. The proton motive force (PMF) is essential for the synthesis of ATP, and it is generated by the electrochemical difference in the proton concentration across the inner mitochondrial membrane. When the proton concentration is more on the outer side, it just moves through the ATP synthase enzyme, which is situated in the membrane from where ADP gets phosphorylated to ATP in the matrix.
Uncouplers are small molecules that increase the permeability of the inner mitochondrial membrane to the protons by bypassing ATP synthase. They allow the oxidation of the substrate on the electron transport chain without ATP formation by reducing PMF. To reestablish the gradient, the cell needs more oxygen and oxidation of NADH to pump the proton out from the matrix. It further limits the ATP level inside the cell because of the change in metabolism so that we can burn more calories without doing any exercise. This turns to be an effective treatment for obesity patients.
The study also proved that this molecule decreases insulin resistance and plays an important role in combating reactive oxygen species. This treatment found to be beneficial to those people suffering from nonalcoholic steatohepatitis (NASH), a type of fatty liver disease.
The research identified that the molecule is non-toxic even at a high level, and it did not affect the satiety center of the mouse. Since the model is successful in mice, we cannot say the same for humans. One such event is the half-life of the drug. Half-life is shorter in mice, whereas longer in humans. As a result, they have tried to modify the drug and made several hundred molecules that are similar to that of the parent molecule. Santos said that the ultimate goal is to promote anti-fat treatment from animal models to humans for the treatment of NASH.
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