Researchers Discover a Safer Way to Make Cells Burn More Calories
The beauty of medication is that one size does not fit all. Take weight loss drugs, for instance. Various classes of weight loss drugs exist to alter appetite, impact absorption, or boost metabolism, but may come with unwanted side effects.
A new class of drugs is being developed, which may nudge cells to burn more calories by changing the cells’ mitochondria (their energy powerhouse).
Researchers have designed experimental substances that push the cell’s mitochondria to use more energy and burn more calories. This new research may offer a novel method of obesity treatment while promoting improved metabolic health.
Obesity impacts individuals globally and increases the risk of chronic conditions, including diabetes, heart disease, and cancer. Several current weight loss drugs require injections and may incur unwanted side effects. Increasing calorie burn may be safer and could offer major public health benefits.
Associate Professor Tristan Rawling of the University of Technology Sydney (UTS) led the study, which was recently published in Chemical Science, the flagship journal of the UK Royal Society of Chemistry.
Mitochondrial Uncouplers
Scientists from UTS and Memorial University of Newfoundland in Canada honed in on substances called "mitochondrial uncouplers." These molecules cause cells to use energy less effectively, releasing some of it as heat instead of changing it into usable power.
Associate Professor Rawling notes, "Mitochondria are often called the powerhouses of the cell. They turn the food you eat into chemical energy, called ATP or adenosine triphosphate. Mitochondrial uncouplers disrupt this process, triggering cells to consume more fats to meet their energy needs".
Rawling likens the process to a hydroelectric system. "It's been described as a bit like a hydroelectric dam. Normally, water from the dam flows through turbines to generate electricity. Uncouplers act like a leak in the dam, letting some of that energy bypass the turbines, so it is lost as heat, rather than producing useful power."
An Unsafe History of Weight Loss Chemicals
Compounds that impede mitochondrial energy production were first discovered about a century ago. However, the initial versions were quite dangerous and caused severe overheating, which could be fatal.
"During World War I, munitions workers in France lost weight, had high temperatures and some died. Scientists discovered this was caused by a chemical used at the factory, called 2,4-Dinitrophenol or DNP," said Associate Professor Rawling.
DNP slows mitochondrial energy production and raises metabolism, according to Rawlings. It was marketed in the 1930’s briefly as one of the initial weight-loss drugs. It was very effective, but was eventually discontinued due to its toxic side effects. The dose needed for weight loss and the lethal dose are too close.
Developing Safer Mild Uncouplers
Safer editions of mitochondrial uncouplers are being created, according to the research. The chemical structure is safely altered in the experimental compounds, letting them control how strongly the molecules increase cellular energy use.
ATP production and cellular damage were not observed in some of the experimental drugs while successfully increasing mitochondrial activity, while others mimicked older toxic substances and produced dangerous uncoupling levels.
In comparing these outcomes, the researchers discovered why safer molecules acted differently. Mild mitochondrial uncouplers reduced the process to a speed that the cells tolerated, which cut the risk of detrimental side effects.
Potential Benefits Beyond Weight Loss
In addition, mild mitochondrial uncouplers may also reduce oxidative stress within cells. This could improve metabolism, slow specific age-related processes, and help protect against neurodegenerative conditions such as dementia.
Despite the research being in its early stages, the findings offer a path for creating a new class of drugs. These new treatments could tackle mitochondrial uncoupling while avoiding the dangerous consequences of previous approaches.
Natural Ways to Burn More Calories:
· Plan short bouts of exercise “snacks” during the day. Get up and move a few minutes every hour. Do some jumping jacks, wall sits, or a plank.
· Keep walking shoes in your car or at your worksite and walk on your lunch hour if time allows.
· Walk inside a big box store or the mall during inclement weather.
· Invest in some stretch bands or light weights to use at home while watching TV.
· Join an exercise class with a friend or neighbor.
Lisa Andrews, MEd, RD, LD
Reference:
Ethan Pacchini, Daniel A. McNaughton, Aaron Pye, Katie A. Wilson, Philip A. Gale, Tristan Rawling. The role of transmembrane proton transport rates in mild mitochondrial uncoupling by arylamide substituted fatty acids. Chemical Science, 2026; DOI: 10.1039/D5SC06530E