Trying to Lose Weight? - It’s a Game of Chemicals

In today’s health-conscious world, everyone knows someone who is trying to lose weight and stay fit.?Regular exercise is one of the preferred ways to do this.?As we know, physical inactivity can lead to weight gain, obesity, obesity-associated diseases and mortality.?However, the exact science behind how exercise connects to the metabolic regulation controlling our weight is still unclear.?How do our body cells sense the exercise and re-program themselves to start using the fat as an energy source, reduce cellular fat storage, and in turn reduce overall body weight?

A group of scientists led by Jonathan Z. Long from Stanford University undertook the challenge of understanding this process (Veronica L. Li, et al, Nature, 2022). They made mice in the laboratory run on a treadmill and collected their blood to look into the unique components present in the blood plasma. They were surprised to see that a metabolite called N-lactoyl-phenylalanine (Lac-Phe) was secreted in the plasma from immune and epithelial cells which are generally known to work for the protection of the body from invading pathogens. This metabolite is generated by the condensation of lactate and phenylalanine catalysed by an enzyme (known as CNDP2).?While looking for the role of this enzyme, they found that two different mutations were present in diabetic patient samples, associated with increased body mass index. This made them wonder whether Lac-Phe, a product of this enzyme, is also important for other conditions like obesity. When scientists artificially administered Lac-Phe to high-fat diet-fed obese mice, it led to reducing their hunger and obesity. On the other hand, when the production of Lac-Phe was blocked in the mice, they gained weight even in the absence of high-fat food. This study suggested that Lac-Phe is regulating the feeding behaviour of mice and reducing their weight through lower food intake.?

Is this molecule present in humans too??Indeed, Lac-Phe mediated response is conserved in mammals including racehorses and humans. This study is the first discovery to show that cells other than muscle cells also respond to physical activity via a secreted metabolite (Lac-Phe) which acts as a signal for altering feeding behaviour and weight loss.

Can this molecule become a new therapy for obesity? Can this become an alternative to the current rigorous exercise regimen? A lot needs to be understood before that – how does Lac-Phe alter the cellular function from storing fat to utilising fat? While a routine exercise alters the levels of about 2000 chemicals, can Lac-Phe alone produce the desired result in absence of other signals? Does Lac-Phe administration lead to any major side-effect? While scientists continue their research on these questions, this recent discovery has raised many hopes that the “weight reduction pill” may see the light of the day sooner than anticipated.?

Written by Ravindra Zirmire