دراسة تكشف كيف تتحكم الساعة البيولوجية في حرق الدهون

A new scientific study has revealed a little-studied protein within the mitochondria that may play a pivotal role in determining how fat cells store and burn energy, in a discovery that clearly links the biological clock, temperature, diet, and the mechanism by which fat cells expend energy for the first time.

The study was published in the journal Science and conducted by researchers from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen, where they focused on a protein known as SLC25A34, found within the mitochondria, which are the energy production centers in cells.

Why is brown fat receiving attention?

Brown fat differs from white fat in its function; it uses fuel to produce heat, and its activity is largely governed by the body's biological clock.

Brown fat activity decreases during sleep, before rising in preparation for waking, but the body may encounter conditions that do not align with this daily rhythm, such as exposure to cold weather in the morning or skipping a meal.

The new findings help explain how the body maintains a daily rhythm of energy consumption while also being able to respond when its energy and heat needs change.

How did the researchers discover the protein?

The research team began by analyzing massive databases to search for proteins present in brown fat in mice, which respond simultaneously to the biological clock and cold exposure.

They found that brown fat contains very low levels of the SLC25A34 protein in mice that lived in warm environments.

However, after exposing the mice to cold for 24 hours, the protein level increased by about 90 times, making brown adipose tissue the most abundant tissue containing it in the body.

How does the "molecular switch" work?

According to the study, signals from the biological clock, food, and temperature converge at the SLC25A34 protein, which regulates the cycle of fat production and oxidation within cells.

During sleep, the biological clock suppresses the activity of the gene responsible for producing the protein through a protein known as REV-ERBα.

But upon waking, or consuming a high-fat diet, or being exposed to cold, this suppression is lifted, and signals for fat breakdown stimulate the production of SLC25A34 through another protein called PPARα.

Subsequently, SLC25A34 transports oxaloacetate into the mitochondria, accelerating the export of materials needed to produce acetyl-CoA in the cytoplasm, allowing the ongoing cycle of fat handling within the cell.

Fasting and insulin elevate the protein

One striking finding in the study is that fasting and insulin, despite their differing effects on fat, together lead to elevated levels of this protein.

The researchers explained that SLC25A34 is essential for both fat building and burning; active brown fat does not only burn existing fat but also builds new fat molecules and then uses them later to produce energy and heat.

In addition to its role in heat production, brown fat helps eliminate fats and sugars present in the blood, adding importance to studying the mechanisms that control its activity.

What happens in the absence of the protein?

When the researchers disrupted the SLC25A34 transporter, fuel burning within brown fat cells decreased, and the tissue's ability to respond to fat burning was significantly weakened in the mice.

To confirm the relevance of this mechanism to humans, the researchers silenced the transporter in brown fat cells taken from four human donors.

The results showed a decrease in fuel burning in cells from three of the four donors, indicating a similar mechanism may exist in humans, although further research is needed to determine the extent to which the results apply fully.

The clock, food, and temperature converge at a single point

Yulia Karavaeva, the lead researcher in the study, stated that previous research typically treated the biological clock, heat response, and food response as separate systems.

However, the study's results suggest that these systems may converge at a single molecular point, which is the SLC25A34 protein.

She added that the researchers have only uncovered a limited part of the picture, noting that the protein is also abundant in the heart and is believed to be linked to metabolic processes in the brain and liver, although its function in these organs remains unclear.

Could the discovery lead to weight loss treatments?

The researchers believe that understanding the relationship between SLC25A34, the biological clock, food, and temperature may eventually open the door to strategies targeting certain metabolic disorders.

However, the study remains in the realm of basic research, and this mechanism has not yet been tested as a treatment in patients.

Additionally, a significant portion of the findings came from experiments on mice and human cells in the lab, so further research is still necessary to determine whether the same mechanism operates in humans to the same degree and whether targeting this protein could indeed lead to safe and effective therapeutic benefits.

Thus, the discovery represents a new step in understanding how fat cells regulate energy consumption, but it does not yet mean there is a proven method for increasing fat burning or weight loss in humans.