Fat - burning molecule

More than 40% of the adult population in the United States and 13% of the world's population are obese. It is often accompanied by many other diseases, including cardiovascular diseases, diabetes and fatty liver dystrophy.

It can be very difficult for obese people to lose weight on their own. Therefore, a pharmacological approach that would help fight obesity will be very useful for society.

A group from Virginia Tech University investigated the properties of a recently discovered small molecule with the properties of a mitochondrial protonophore – BAM15.

We could not find how this abbreviation stands for. If you want, you can use its nomenclature name: (2-fluorophenyl) {6 - [(2-fluorophenyl) amino] (1,2,5-oxadiazolo [3,4-e] pyrazine-5-yl)} amin :) – VM.

It reduces the mass of adipose tissue in mice without affecting food intake and muscle mass and without increasing body temperature. In addition, the molecule reduces insulin resistance and has a beneficial effect on oxidative stress and inflammation.

Mitochondria are also called cell power plants. The organelle generates ATP and provides body movement and other biological processes.

To produce ATP, mitochondria oxidize nutrients and establish a proton-driving force (PMF). PMF is formed by the proton gradient – the difference in concentration outside the inner membrane and in the mitochondrial matrix, which promotes the movement of protons inside the organelle. ATP is created whenever protons pass through the membrane and come into contact with the enzyme ATP synthase. built into the membrane. Consequently, the oxidation (burning) of nutrients is associated with the synthesis of ATP.

This means that reducing PMF can enhance cell respiration. Mitochondrial protonophores are small molecules that rush into the mitochondria to help the cell breathe. In fact, they alter the metabolism in the cell, so that the body burns more calories without doing any exercise.

Mitochondrial protonophores transport protons into the matrix, bypassing ATP synthase. To restore the gradient, protons must be removed from the mitochondrial matrix. To do this, the organelle begins to burn energy at a level higher than usual.

Thus, these molecules can change the metabolism of the cell. The researchers decided to make sure that the new drug reaches the desired target and that it is safe. In a series of studies on mice, they found that BAM15 is non-toxic even in high doses and does not affect the saturation center in the brain. Animals treated with BAM15 received the same amount of food as in the control group, but lost fat mass.

Other benefits of BAM15 include:

• Reducing blood sugar and insulin levels regardless of weight loss.
• Improving the sensitivity of skeletal muscles to the effects of insulin. Skeletal muscle insulin resistance is a major risk factor for type 2 diabetes.
• Reducing fat accumulation in general by limiting fat accumulation in the liver, kidneys and blood. The accumulation of too much fat in the liver, kidneys or blood can damage organs and lead to heart disease.

Figure from an article by Axelrod et al. BAM15‐mediated mitochondrial uncoupling protects against obesity and improves glycemic control, published in the journal EMBO Molecular Medicine.

One of the side effects of previously studied drugs with mitochondrial protonophores was an increase in body temperature. Using a rectal probe, the researchers monitored the temperature of mice given BAM15. They found no changes in the body temperature of the animals.

But there is a serious problem regarding the application of BAM15. Half-life (the time during which the drug is still effective) it was relatively short, but sufficient for mice. For oral administration in humans, the half-life should be much longer.

Despite the great potential of BAM15 in mice, the drug will not necessarily be effective in humans – at least not in the same form. The researchers' further goal is to transfer anti-fat treatment from animal models to the treatment of obesity and related diseases in humans.

It is worth adding that BAM15 molecules are also unique antioxidants, they are able to minimize the accumulation of reactive oxygen species and reduce oxidative stress in the body, ultimately leading to neurodegeneration and aging.

Article by S.J.Alexopoulus et al. Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice published in the journal Nature Communications.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru According to Virginia Tech Daily: Virginia Tech drug researcher develops 'fat burning' molecule that has implications for treatment of obesity.