In breakthrough research on weight loss, researchers have recently identified a small mitochondrial uncoupler named BAM15 that decreases mice's body fat mass without altering food intake, muscle, mass, or increase in body temperature. Furthermore, the molecule reduces insulin resistance and has favorable effects on oxidative stress and inflammation.
Knowing that mitochondrial uncouplers could alter a cell's metabolism, the authors of the research wanted to ensure that the drug was reaching its desired targets and was deemed safe to use. Through an array of mouse studies, the researchers discovered that BAM15 is neither toxic nor does it affect the gratification center in the brain, which sends signals to our body to determine a feeling of being hungry or full.
Many anti-obesity drugs in the past would initially tell the body to stop eating. However, as a result, people would experience rebound reactions and eat more. In the BAM studies with mice, the small creatures ate the same amount as the control group, but still had losses in fat mass.
The findings of the study were published in the journal Nature Communications on May 14, 2020. The researchers believe their paper holds a promise for future treatment and prevention of obesity, diabetes, and especially nonalcoholic steatohepatitis (NASH). The said condition is a kind of fatty liver disease marked by inflammation and fat accumulation in the liver. Moreover, the ailment is expected to become the leading cause of liver transplants in the United States in the next few years.
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The Problem With Obesity
According to the CDC's National Center for Health Statistics, the age-adjusted prevalence of obesity in adults was 42.4 percent from 2017 to 2018. Moreover, there were no significant differences found between men and women among all adults or by age group.
Additionally, obesity influences more than 40 percent of adults in the United States and about 13 percent of the global population. Various diseases are correlated with obesity, particularly cardiovascular disease, diabetes, and fatty liver disease. Having underlying conditions attributed to obesity makes the illness more difficult for physicians to treat.
According to one of the authors and a chemistry professor, Webster Santos, despite being one of the biggest health problems in America, people find it hard to lose weight and tend to keep off it. Furthermore, the Cliff and Agnes Lilly Faculty Fellow of Drug Discovery in the College of Science at Virginia Tech adds that a drug might help address the problem and benefit society.
Mitochondrial Uncouplers
Mitochondrial uncouplers are tiny molecules that go to the mitochondria to help the cells to oxidize more. The mitochondria are commonly known as cell powerhouses. The organelle produces ATP, a molecule that acts as the energy currency of the cell. It also powers body movement and other biological courses in the body that allow it to function correctly.
To produce ATP, nutrients need to be burned, and a proton motive force (PMF) should be rooted within the mitochondria. Santos explains that anything that lessens the PMF has the capability to increase respiration.
Furthermore, mitochondrial uncouplers carry protons into the pattern by bypassing ATP synthase, which escapes the PMF. To restore the gradient, protons should be transported out of the mitochondrial matrix. Because of this, the cell begins to burn fuel at higher levels.
Another side effect of earlier mitochondrial uncouplers was heightened body temperature. Researchers then measured the body temperature of mice who were fed BAM15 using a rectal probe. Consequently, they found no alteration in body temperature.
Another issue with BAM15 is its half-life or the length of time a drug is deemed effective. In mouse modes, it was found to be relatively short. In oral dosages for humans, the optimal half-life would be much longer.
According to researchers, even if BAM15 has shown potential in mouse models, the drug won't necessarily be successful in humans, at least not using the same molecule. Further studies are warranted to learn more about the use of the molecule in humans.
Finally, the Santos lab's ultimate goal is to convert the anti-fat treatment from animal models to treatment for NASH in humans. So far, the lab has used its better compounds in animal models of NASH, which have given off positive results when used as anti-NASH compounds in mice.
