Could the 'Anti-hunger' Molecule Be the Miracle Weight Loss Cure of the Future?

Obesity is a growing epidemic. More than 4 in 10 people in the United States are classified as obese, according to the Centers for Disease Control and Prevention (CDC). Research notes that since 1980 the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most others.

The rising pandemic of obesity is a major public health crisis. Obesity is linked with several chronic diseases, including heart disease, stroke, type 2 diabetes, and certain types of cancer. Furthermore, it costs billions of dollars in healthcare spending.

People who are overweight or obese are often advised to decrease their calorie intake and increase their energy expenditure to lose weight. This calorie deficit can be achieved by modifying the diet and undertaking more physical activity.

Exercise and physical activity that moves the body is essential for overall health. Guidelines recommend that adults get 150 minutes of moderate-intensity physical activity each week, plus 2 days of muscle-strengthening activity.

Besides supporting health, exercise increases the body's energy needs. Burning calories may directly affect body weight and fat loss, and it can increase muscle mass and metabolism. Exercise also helps balance hormones that can affect body weight like cortisol, insulin, thyroid hormones, testosterone, and progesterone.

But new research shows that exercise may also have other biochemical benefits that help combat obesity and its related conditions.

A recent study led by scientists from Stanford University School of Medicine and Baylor University has found that a naturally occurring molecule may help to reduce hunger and promote weight loss.

The weight loss effects of exercise

New research found that exercise induces a molecule that suppresses appetite.

The molecule is called lac-phe, and its levels increase significantly directly following exercise. The compound could check appetite, which could reduce obesity and overweight in the long term.

The team sets out to understand how exercise affects body weight and blood sugar control. They wanted to look at the specific molecules and biological pathways involved. They used something called a "metabolomics" approach to look at molecules that appeared or disappeared in the blood of experimental mice before and after they exercised on a treadmill. In other words, the natural ebb and flow of the body's chemicals during exercise.

The scientists used a mass spectrometer machine to identify the presence of various molecules in tissues or blood samples based on their weights. They could track the concentration of various molecules, which allowed them to see how exercise caused them to rise or fall by comparing data from before and after exercise.

They identified that a molecule measuring 236 on the mass spectrometer had the largest changes in concentration. This is how they identified the spike in lac-phe.

It was then important to understand if the spike only appeared in mice or was it universal across species. The team also needed to determine if the spike was caused by exercise or could be due to something else, such as stress.

Racehorses, mice, and humans

To find further answers, the team then turned to racehorses. The scientists visited a racing track and obtained blood samples from horses. They then ran another mass spectrometry experiment and were excited to find the same spike in the unknown molecule with a mass of 236.

At this point, the team considered independent research that was also being undertaken at Stanford University. Genetics researchers measured how different molecules increased in human participants during and following exercise. The results also revealed spikes in a molecule with a mass of 236.

Furthermore, the genetics team had analyzed its chemical formula, finding it was a combination of lactate and phenylalanine.

So, it seems that lac-phe appears post-exercise in the same way in mice, racehorses, and humans.

What is lac-phe?

Lac-phe is a molecule that combines lactate and phenylalanine, hence the name.

Lactate or lactic acid is an organic acid that the body produces during anaerobic respiration, meaning in the absence of oxygen. As the body breaks down glucose to generate cellular energy (ATP), it produces lactate.

If you've ever sprinted or exercised intensely, you'll recall the burning, uncomfortable sensation in your muscles. That's the effect of lactate.

Phenylalanine is an essential amino acid and a building block of protein. It occurs naturally in the body, in many protein-rich foods, and the artificial sweetener aspartame.

As you exercise, you generate lactate. This spike triggers a protein called CNDP2 to combine with the lactate and form lac-phe. CNDP2 exists in numerous cells and is highly active in immune cells.

When obese mice were treated with lac-phe, it reduced their appetites by around 30%. In turn, this reduces their body weight and fat and improves their glucose tolerance. The authors noted that these effects were similar to a reversal of diabetes.

However, mice that lacked the CNDP2 gene were unable to produce lac-phe. Therefore, they didn't lose as much weight on the exercise plan as the control mice.

The scientists surmise that the lac-phe pathway could be responsible for approximately 25% of the weight loss effects of exercise.

Future directions

The results of the research improve the understanding of how exercise can affect hunger and may indirectly affect weight beyond burning calories. However, although these findings are exciting, it's still early days, and more research is required to explore these mechanisms further.

The next big challenge is to see if the discovery can be translated into medications that could control appetite. Firstly though, scientists must further discern how lac-phe affects hunger signals and identify the brain receptors involved in this process.

If scientists can fully comprehend the processes involved in exercise and appetite suppression, they are one step closer to helping people improve their health and tackling the obesity epidemic.

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