A high-fat diet causes mitochondrial fragmentation and white adipocyte dysfunction due to activation of RaIA.

Obesity has become a global epidemic. This is evidenced by figures such as those presented in the World Obesity Atlas 2023, prepared by the World Obesity Federation, which estimates that in 2035, 4 billion people will be overweight or obese. However, in addition to diet, exercise and lifestyle, scientists have realized that this disease is also associated with various metabolic disorders. In this sense, researchers from the University of California, San Diego, published a study in the journal Nature Metabolism that shows how obesity affects mitochondria.

mitochondrial dysfunction It is a sign of obesity, insulin resistance and fatty liver disease in both humans and rodents. In this paper, the researchers show that feeding a high-fat diet (HFD) causes mitochondrial fragmentation in the inguinal white adipocytes of male mice, which divide into many smaller, inefficient mitochondria that burn less fat.

Moreover, they also noticed that this effect powered by one RaIA molecule, whose functions include the destruction of mitochondria when they do not function properly. RalA expression and activity are increased in white adipocytes after HFD.

In accordance with Alan Saltiel, PhD, Professor, Department of Medicine, UC San Diego School of Medicine“Calorie overload due to overeating can lead to weight gain and also trigger a metabolic cascade that reduces energy burning, further exacerbating obesity. “The gene we identified is a fundamental part of the transition from a healthy weight to obesity.”

In cases of caloric imbalance such as obesity, the ability of fat cells to burn energy begins to deteriorate, making it difficult for these people to lose weight. However, How do these metabolic disorders begin? This is one of the greatest mysteries of this disease.

The link between obesity and mitochondria

Research in this area is currently very active, with various studies linking obesity to changes in mitochondrial function. On the one hand, it is known that causes inflammation and oxidative stress

and both processes can contribute to the dysfunction of these cells. Likewise, insulin resistance obesity is associated with functional problems in mitochondria. Now, in this new study, in addition to understanding the role of RaIA, they were also able to develop strategies for protection.

“In essence, chronic activation of RaIA appears to play a fundamental role in suppressing energy expenditure in adipose tissue in obesity,” says Saltiel. “By understanding this mechanism, we are getting closer to develop targeted therapy it can help address weight gain and associated metabolic dysfunction by increasing fat burning,” he emphasizes.

This study shows how delete the gene associated with RaIA Researchers were able to protect mice from diet-induced weight gain. Additionally, by analyzing the biochemical process, they found that some of the proteins affected by RaIA in mice are similar to human proteins that are associated with obesity and insulin resistance, suggesting that similar mechanisms may cause obesity.

“Direct comparison of what we found with actual clinical results highlights the relevance of our findings to humans and suggests that we may be able to help treat or prevent obesity by targeting the RaIA pathway with new treatments,” says Saltiel. “We are just beginning to understand the complex metabolism of this disease, but the future possibilities are exciting,” he concludes.

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