A group of researchers developed a fat-burning molecule and applied it to mice models. The molecule was found to reduce body fat in mice but kept their appetite and muscle mass intact. This could be utilized to create novel overweight therapies.
The novel fat-burning molecule was developed by researchers at Virginia Polytechnic Institute and State University (VT), a public research university in the US. Their molecule could help burn body fat mass without adversely impacting other metabolic factors. The molecule would not influence food intake, muscle mass, and body temperature, according to experiments with mice. They published their findings in the journal Nature Communications.
The Prevalence of Obesity and Overweight
According to the World Health Organization of the United Nations, obesity and overweight are health conditions characterized by an abnormal or excessive accumulation of body fat, which may impair their overall health. Both conditions can occur in people of all ages and each affected individual may be at risk of numerous illnesses, including diabetes, hypertension, heart disease, and kidney problems. Because of health risks, physicians always advise their patients to eat healthy food choices, exercise regularly, and live a good lifestyle to avoid weight management issues.
In 2016, over 1.9 billion adults aged 18 years and older were overweight and out of that, more than 650 million were obese. By gender, 11% of adult males and 15% of adult females were obese, which translated to 13% of the world's adult population being obese, while 39% of the world's adult population was considered overweight. For children, estimates showed that more than 340 million children and teenagers, aged 5 to 19 years, were either overweight or obese.
By 2019, the prevalence of obesity and overweight among children increased substantially. Both conditions were considered a common problem in high-income territories, but factors empowered the prevalence in low- and middle-income nations. The prevalence in non-high-income nations was particular in urban settings. About 38.2 million children younger than five years were either obese or overweight. An increase of almost 24% in the overweight children population since 2000 was identified in Africa, while nearly 50% of children younger than five years in Asia were either obese or overweight.
Meanwhile, Statista, a German portal for statistics, showed that as of 2019, 5.9% of children younger than five years, 20.6% of children between five and nine years, 17.3% teenagers between 10 and 19 years, and 38.9% of adults 18 years and older were estimated to be overweight. Although the main description of obesity and overweight is the accumulation of body fat, the main cause has never been specified, making both conditions complex. Cases differ from one another.
Scientific studies have obtained insights into obesity and overweight. Some results hint at the genetic disposition of certain people to accumulate more body fat than others, while other findings link the significance of external factors that prevent people from maintaining an ideal weight. External factors like urbanization, sedentary lifestyle, and unhealthy food choices are correlated to weight problems.
Novel Fat-Burning Molecule Developed
At VT, researchers formulated a new molecule that could burn body fat mass without burning muscle mass or affecting food intake. They tested this molecule in mice models and found its efficacy in reducing total body fat. They also discovered that the molecule lowered resistance to insulin and decreased inflammation and oxidative stress. If proven to be safe for humans, the molecule might pave the way for newer therapies of obesity. However, it must be reformulated for the human body.
"Obesity is the biggest health problem in the United States. But it is hard for people to lose weight and keep it off; being on a diet can be so difficult. So, a pharmacological approach, or a drug, could help out and would be beneficial for all of society," said Webster Santos, lead author of the study and professor of chemistry at VT.
In the study, the molecule was based on the known science about the mitochondrion, an organelle in cells. The organelle is known for its ability to generate adenosine triphosphate or ATP – the energy currency of cells. But as powerhouses of cells, mitochondria need to burn nutrients and a proton motive force or PMF to generate ATP. With that basic knowledge, complex organisms like humans require food to provide the nutrients cells need to generate energy.
The burning of nutrients is an eternal partner in the energy production of mitochondria. The PMF is produced from either a proton gradient or space within the inner membrane. ATP is generated when protons pass through an enzyme called ATP synthase, embedded in the membrane. So, anything that affects the PMF can influence cellular respiration. Mitochondrial uncouplers are small molecules capable of influencing respiration. These uncouplers can alter cellular metabolism to burn calories without physical exertion.
As their name suggests, uncouplers bring protons to the mitochondrial matrix but bypass the ATP synthase. The unorthodox function of the uncouplers can result in the burning of nutrients at a higher rate. This bypass technique from uncouplers is what inspired researchers to create the BAM15 molecule – a potential solution for burning body fat without causing ill effects.
Researchers used mice models and exposed them to BAM15. Experiments showed that the molecule was not toxic even in high doses. The molecule was also not impactful to the brain's satiety center, which led to no changes in food intake. Due to the molecule's zero influence on satiety, mice would still eat normally unlike what many anti-fat drugs do. Normally, those drugs would fool the satiety center to stop food intake. The manipulation of satiety might be good at first, but once the person stops taking the drugs, they would likely rebound and eat more than they used to.
Another notable side effect missing in BAM15 was the increase in body temperature. Previously developed uncouplers would increase the subject's body temperature. However, mice administered with BAM15 had normal temperature levels. Despite these positive findings, some issues need to be resolved before BAM15 becomes applicable to humans. First, the half-life or duration of the molecule's efficacy in humans was found longer than in mice. Second, the molecule's potential in mice might not be as good in humans. If the molecule's structure could be changed, researchers might create a version compatible with humans.
The main goal of this research is to create a new treatment for non-alcoholic steatohepatitis or NASH. The molecule is being optimized for NASH because of the condition's strong association with obesity, prediabetes, and diabetes.