Paving the Way for the Development of Obesity and Diabetes Medications: Discovery of the 'Fat Burning Coordinator'

Researchers have discovered a protein that acts as a molecular switch, helping fat cells coordinate energy burning with the biological clock, environmental temperature, and food quality, in a finding that may open a new pathway for understanding metabolic regulation and possibly developing treatments for obesity and diabetes.

The study was conducted by researchers at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen in Denmark.

The study, published in the journal Science, showed a less-studied protein known as SLC25A34, which is found inside mitochondria, the energy production centers in cells, plays a pivotal role in determining how fat cells store and consume energy.

A study revealed that the protein known as the type 1 cannabinoid receptor (CB1) may be a key factor in explaining why some individuals respond to chronic stress with anxiety and depression.

The research focused on brown fat, a type of adipose tissue that not only stores energy but also burns it to produce heat and maintain body temperature, with the activity of this fat changing throughout the day according to the biological clock, decreasing during sleep and then starting to rise before waking.

However, the body sometimes faces conditions that do not align with this regular schedule, such as sudden exposure to cold or fasting, which forces it to increase energy consumption at times not planned by the biological clock.

The study examined large databases for proteins present in brown fat in mice, which respond simultaneously to cold and the biological clock.

The researchers found only two proteins that met these criteria, one being the well-known protein "UCP1" responsible for heat production, and the other "SLC25A34" whose function was unclear.

In mice that lived in comfortable temperatures, the levels of this protein in brown fat were extremely low compared to most body tissues, but after exposure to cold for 24 hours, its levels increased by about 90 times, making brown fat the tissue with the highest content of it in the body.

Experiments revealed that the gene responsible for producing the protein is regulated by three different mechanisms; during sleep, a protein linked to the biological clock called "REV-ERB alpha" suppresses the gene's activity, before its effect diminishes just before waking.

A scientific study issued by the American universities of Michigan and Maryland revealed the GLUK2 protein responsible for mammals' sensation of a drop in temperature.

However, exposure to cold can override this temporal control, allowing the body to increase protein production at any time if it needs to generate more heat. It has also been shown that fats coming from body stores or from food can activate the gene via another regulatory protein called "PPAR-alpha."

The lead researcher of the study, Zach Gerhart-Hines, stated that the biological clock and the response to heat and food are usually viewed as separate systems, but the results suggest that a transporter present within the mitochondria can respond to all three systems together.

He added that this could allow for future considerations of treatments that alter the timing and manner in which the body burns fuel, rather than being limited to the mechanisms currently used in treating obesity and diabetes.

The study showed a result that seemed contradictory at first glance, as both fasting, which drives the body to burn fat, and insulin, which helps store it, led to increased protein levels.

Researchers say the explanation lies in the fact that active brown fat produces new fat molecules and then burns them, in a cycle that helps generate heat and eliminate fats and sugars present in the blood.

Researchers suggest that the protein maintains the continuity of this cycle by transporting a molecule called "oxaloacetate" into the mitochondria. When they disrupted the protein, fuel burning in brown fat cells decreased, and the response to fat burning in mice weakened significantly.

Researchers recorded a similar effect in brown fat cells taken from humans, as silencing the gene led to a reduction in energy consumption in cells from 3 out of 4 donors.

Analysis of data from 24 clinical studies showed that individuals with higher levels of protein in subcutaneous white fat were, on average, lighter and had better metabolic health indicators.

However, researchers emphasized that this relationship does not prove that higher protein levels cause improved metabolic health, nor has the study yet directly demonstrated that the protein transports the oxaloacetate molecule, or whether its disruption affects long-term health.