Deleting a Gene to Say Goodbye to Obesity

Obesity has long been a major killer of health. According to the latest research report, as China's economy continues to improve, the number of obese people in China has also been increasing. By the end of 2023, the overweight rate for men was 41.1%, and for women, it was 27.7%. Whether it's for health reasons or to pursue a better self-image, weight loss has become a long-standing hot topic. However, losing weight is difficult, and only those who have truly lost weight can understand. Therefore, for obese individuals, the "easy-to-lose-weight" physique, where one can eat whatever they want without gaining weight, is truly enviable.

A recent study from the University of California, San Diego, suggests that obesity leads to mitochondrial dysfunction in fat cells, driven by a specific gene. Inactivating this gene in mice prevented obesity, suggesting a new therapeutic approach.

In a study published in Nature Metabolism on January 29, 2024, researchers found that when mice were fed a high-fat diet, mitochondria in their fat cells split into smaller mitochondria, reducing their ability to burn fat. Furthermore, they discovered that this process was controlled by a gene. By deleting this gene from mice, they instantly became "easy-to-lose-weight", and even when they ate the same high-fat food as other mice, they were protected from becoming overweight.

Dr. Alan Saltiel, a professor of medicine at the University of California San Diego School of Medicine, said: "Caloric overload from overeating leads to weight gain and triggers a metabolic cascade that reduces energy burning and exacerbates obesity. The gene we identified is a critical part of the transition from healthy weight to obesity."

Research Findings and New Therapeutic Ideas Researchers fed mice a high-fat diet and measured its effects on the mitochondria in their fat cells, which are structures within cells that help burn fat. They discovered an unusual phenomenon. After consuming a high-fat diet, the mitochondria in the mice's adipose tissue split into many smaller, less efficient mitochondria, burning less fat.

In addition to discovering this metabolic effect, they found that it was driven by the activity of a single molecule called RaIA. RaIA has many functions, including helping to break down mitochondria when they malfunction. The new research shows that when this molecule is overactive, it interferes with the normal function of mitochondria, triggering obesity-related metabolic problems.

"Essentially, chronically activated RaIA seems to play a key role in suppressing energy expenditure in obese adipose tissue," Saltiel said. "By understanding this mechanism, we are one step closer to developing targeted therapies to address weight gain and related metabolic disorders by increasing fat burning."

By deleting the gene associated with RaIA, researchers were able to protect mice from diet-induced weight gain. Delving deeper into the underlying biochemistry, researchers found that some proteins affected by RaIA in mice were similar to proteins associated with human obesity and insulin resistance, suggesting that a similar mechanism may contribute to human obesity.

"The direct comparison between our basic biology findings and the actual clinical outcome underscores the relevance of these findings to humans and suggests that we may be able to treat or prevent obesity with new therapies targeting the RaIA pathway," Saltiel said. "We're only beginning to understand the complex metabolism of this disease, but the future possibilities are exciting."

Key points emphasized in the translation:

• Clarity and conciseness: The translation aims to maintain the clarity and conciseness of the original text while ensuring accurate scientific terminology.
• Scientific accuracy: The translation accurately conveys the scientific concepts, such as mitochondria, metabolism, and gene function.
• Relevance to humans: The translation highlights the potential implications of the research for human health and the development of new treatments for obesity.