Obesity affects more than 40% of the adult US population and more than 13% of the world population. Obesity is a very difficult and indispensable disease to treat due to diseases such as heart diseases, diabetes, and fatty liver.
“Obesity is the biggest health problem in the United States,” said Webster Santos, professor of chemistry, member of the Virginia College of Technology Science, Cliff and Agnes College’s Drug Discovery Board. However, losing weight and keeping it sustainable; Diets are very difficult for humans. For this reason, helping people with a pharmacological approach, perhaps with a medicine, will be very beneficial for all segments of the society. says.
Recently, Santos et al. Identified a small mitochondrial decomposer called BAM15 that reduced body fat mass in mice without affecting food intake and muscle mass or increasing body temperature. It’s also a molecule that has beneficial effects on oxidative stress and inflammation while reducing insulin resistance. The findings, published in the journal Nature on May 14, 2020, show promise in the future for the treatment and prevention of diseases such as nonalcoholic steatohepatic (NASH), which is a form of liver fat due to obesity, diabetes, inflammation and fat accumulation. In the next few years, this is expected to be the leading cause of liver transplants in the USA.
We burn more calories without exercise
Mitochondria are commonly referred to as the powerhouse of the cell. Mitochondria are organelles that produce ATP, which supports the body by providing power for the movement of the body and the proper functioning of other biological processes, and ensures the energy continuity of the cell. To produce ATP, the nutrients must be burned and, accordingly, the proton-motivated force-PMF) must be created within the mitochondria. PMF consists of proton bias caused by the difference between the high density of protons outside the mitochondrial inner membrane and the low density of protons in the matrix – the liquid in the mitochondria – or in the space within the inner membrane.
With each passage of protons over the enzyme called ATP synthase, which is embedded in the membrane, the cell synthesizes ATP. As a matter of fact, food oxidation, also known as food burning, results in ATP synthesis.
“So anything that reduces PMF has the potential to increase respiration,” said Santos, Fralin Institute of Life Sciences and the Virginia Center for Drug Discovery Technology. Mitochondrial decomposers are small molecules that enter the mitochondria, helping the cell to breathe more. They effectively alter cell metabolism so that we burn more calories without exercise. ” says.
Mitochondrial decomposers carry protons to the matrix, bypassing the ATP synthase that functions in the PMF direction. To restore the bias in question, protons must be expelled from the mitochondrial matrix. As a result, the cell starts burning higher levels of fuel than is required.
Knowing that these molecules could change the metabolism of the cell, the researchers worked to make sure that the drug could reach the desired target and, above all, that it was safe. Through a series of mouse studies, the researchers found that BAM15 is not toxic even at high doses, nor does it affect the satiety center in the brain that tells our bodies we are hungry or full.
We’re looking for the same type of molecule
In the past, many debilitating medications told your body to stop eating. But this was counterproductive and as a result, patients ate more. In the BAM15 mouse studies, the experimental group animals experienced weight loss despite being fed the same amount of food as the control animals.
Another side effect of the previously used mitochondrial decomposers was increased body temperature. Using a rectal probe, the researchers measured the body temperature of mice fed BAM15 and did not detect a change in body temperature. However, a problem arose with the half-life of BAM15. The half-life, or time the drug is still effective, is relatively shorter in mice, while the ideal half-life is much longer in humans with oral intake. Despite the serious potential of BAM15 in mice, the drug – at least the exact same molecule – is not expected to be as successful in humans.
“First of all, we are looking for a molecule of approximately the same type, but this molecule has to stay in the body long enough to take effect. We’re making some fine adjustments to the chemical structure of the compound. So far, we’ve got several hundred molecules that are similar in this way, ”says Santos.
We want to use these mitochondrial decomposers for more.
Santos Laboratory’s penultimate goal is to switch the debilitating treatment method from animal models to NASH treatment in humans. The lab also used its better compounds that have proven effective as anti-NASH compounds in mice in NASH animal experiments.
Kyle Hoehn, Associate Professor of Biotechnology and Biomolecular Sciences at the University of New South Wales, Australia and a faculty member in the Department of Pharmacology at the University of Virginia, continues to work with Santos. Hoehn is a metabolic physiologist who studies animals. Santos and Hoehn have worked together for years and have now formed a biotech company together.
Founded by Santos and Hoehn in 2017, Continuum Biosciences aims to develop ways our bodies fight against burning fuel and storing nutrients as fat as we age. These promising NASH therapy compounds are licensed by their company and patented by Virginia Technology.
The company wants to use the aforementioned mitochondrial decomposers for more than obesity and NASH. These molecules also have a unique anti-oxygen effect in our body that reduces the accumulation of reactive oxygen species – oxidative stress – that results in neural deterioration and aging.
“By simply reducing aging, you can reduce the risks of Alzheimer’s or Parkinson’s disease. Diseases due to all reactive oxygen species or inflammation can benefit from mitochondrial decomposers. That is how we can see the trend. ” says