A study from the University of California, San Diego shows that the key mechanism for obesity in our cells lies in the mitochondria
According to the WHO (World Health Organization), obesity is a chronic disease, characterized by an increased percentage of body fat, which is associated with a higher health risk. The number of people with obesity has almost tripled since 1975, creating a global epidemic.
It is often said that obesity is due to too many calories and lack of exercise, but that is the same as saying death occurs from cardiac arrest. Although lifestyle factors such as diet and exercise play a role in the development and progression of obesity, scientists are beginning to understand that obesity also results from intrinsic metabolic disorders.
Overweight, obesity and morbid obesity
The OKiss works 16.5% of men and 15.5% of women in Spainaccording to the European Health Survey in Spain in 2020. In addition, overweight and obesity affect health 39% of girls and 38% of boys aged 7 to 9 years. Obesity affects more than 40% of adults in the United States. You are considered overweight if your BMI (body mass index) is between 25 and 30. With the metric system applies The formula for BMI is weight in kilograms divided by height in meters squared..
Also according to the WHO, there are three stages of this disease: obesity grade I (BMI from 30.0 to 34.9 kg/m2), grade II (35.0 to 39.9 kg/m2) and grade III, respectively morbid obesity (BMI equal to or greater than 40.0 kg/m2). This extreme form of obesity is the most serious category within the overweight classification.
The vicious circle of obesity and mitochondria
Researchers at the University of California, San Diego School of Medicine have shed new light on the effects of obesity on our mitochondria, the energy-producing organelles in our cells.
In a study published in Nature Metabolism, researchers found that when mice were fed a high-fat diet, the mitochondria in their fat cells split into smaller mitochondria with less ability to burn fat. Furthermore, they discovered that this process is controlled by a single gene. By deleting this gene in mice, they managed to protect them from excessive weight gain, even when they were fed the same high-fat diet as other mice.
“Calorie overload from overeating can lead to weight gain and also triggers a metabolic cascade that reduces energy burning and further worsens obesity,” says Dr. Alan Saltiel, professor at the UC San Diego School of Medicine. “The gene we identified is a critical part of the transition from healthy weight to obesity.”
The cause of obesity
Obesity occurs when the body accumulates too much fat, which is stored primarily in adipose tissue. Adipose tissue is necessary: It typically provides important mechanical advantages by cushioning and insulating vital organs. It also has important metabolic functions, such as releasing hormones and other cell signaling molecules that instruct other tissues to burn or store energy.
Calorie imbalances like obesity happen when fat cells begin to lose the ability to burn energy, which is one of the reasons people with obesity can find it difficult to lose weight. How these metabolic disorders arise is one of the biggest mysteries associated with obesity.
To answer this question, researchers fed mice a high-fat diet and measured the effects of that diet on their fat cells’ mitochondria, structures within the cells that help burn fat. They discovered an unusual phenomenon. After consuming a high-fat diet, mitochondria in some parts of the mice’s fatty tissue fragmented and divided lots of smaller, inefficient mitochondria that burned less fat.
The molecule that destroys mitochondria
They discovered not only this metabolic effect, but also that it is controlled by the activity of a single molecule called RaIA. RaIA has many functions, including helping to break down mitochondria when they fail. New research suggests that when this molecule is hyperactive, it interferes with the normal functioning of mitochondria, triggering the metabolic problems associated with obesity.
“Essentially, chronic activation of RaIA appears to play a crucial role in suppressing energy expenditure in obese adipose tissue,” says Saltiel. “By understanding this mechanism, we are one step closer to developing targeted therapies that could combat weight gain and associated metabolic disorders by increasing fat burning.”
By deleting the gene associated with RaIA, the researchers were able to protect the mice from diet-induced weight gain. As the researchers delved deeper into the biochemistry, they discovered that some of the proteins affected by RaIA in mice were comparable to human proteins linked to obesity and insulin resistance, suggesting that similar mechanisms could trigger obesity.
“The direct comparison between the basic biology we discovered and the actual clinical results underscores the relevance of the results to humans and suggests that we may be able to help treat or prevent obesity by targeting new therapies to the RaIA signaling pathway says Saltiel. “We are just beginning to understand the complex metabolism of this disease, but the future possibilities are exciting.”
REFERENCE
Obesity leads to mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation
Photo by Karolina Grabowska