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Mitochondria Diet Genetic Research Metabolic Dysfunction

Obesity “Dismantles” Mitochondria

4 months, 3 weeks ago

3588  0
Posted on Jan 29, 2024, 4 p.m.

The rates of obesity have nearly tripled since 1975, this alarming shift has resulted in a worldwide epidemic. Most certainly lifestyle factors such as diet, nutrition, exercise, physical activity, and sedentary time play critical roles in both the development and progress of obesity, but scientists have to understand that obesity is also associated with intrinsic metabolic abnormalities.

Researchers from the University of California-San Diego recently published a paper in Nature Metabolism shedding new light on how obesity can affect our mitochondria, which are the all-important energy-producing structure of our cells. The paper describes how when mice were fed a high-fat diet (HFD), mitochondria within their fat cells broke apart into smaller mitochondria with a reduced capacity for burning fat. This process was discovered to be controlled by a single gene, and deleting this gene from the mice protected the animals from excess weight gain, even when fed an HFD.

"Caloric overload from overeating can lead to weight gain and also triggers a metabolic cascade that reduces energy burning, making obesity even worse," said Alan Saltiel, PhD, professor in the Department of Medicine at UC San Diego School of Medicine. "The gene we identified is a critical part of that transition from healthy weight to obesity."

More than 40% of American adults are affected by obesity which occurs when the body accumulates too much fat, which is primarily stored in adipose tissue. This tissue normally provides mechanical benefits by cushioning our vital organs and providing insulation. But it also has other metabolic functions like releasing hormones and other signaling molecules that instruct other tissue to burn/store energy. 

The ability of fat cells to burn energy starts to fail in cases of caloric imbalances such as obesity, which is one of the reasons why it can be difficult for those with obesity to lose weight. Exactly how these metabolic abnormalities start is one of the unknown surrounding obesity. This study measured the impact of an HFD on mice fat cell mitochondria to gain new insights into metabolic abnormalities. 

According to the researchers, they discovered an unusual phenomenon, after consuming an HFD mitochondria in parts of the animal’s adipose tissue underwent fragmentation and were observed to split into many smaller and ineffective mitochondria that burned less fat. In addition to discovering this metabolic effect, the researchers also discovered that it is driven by the activity of a single molecule called RalA. 

This molecule has many functions such as breaking down mitochondria when they malfunction. The researchers believe that when it is overactive, RalA interferes with the normal functioning of mitochondria, triggering the metabolic issues associated with obesity. 

"In essence, chronic activation of RalA appears to play a critical role in suppressing energy expenditure in obese adipose tissue," said Saltiel. "By understanding this mechanism, we're one step closer to developing targeted therapies that could address weight gain and associated metabolic dysfunctions by increasing fat burning."

Deleting the gene associated with RalA was found to protect the mice against diet-related induced weight gain. Further investigation found that some of the proteins affected by RalA in mice are analogous to human proteins that are also associated with obesity and insulin resistance. These findings suggest that there may be similar mechanisms driving human obesity. 

"The direct comparison between the fundamental biology we've discovered and real clinical outcomes underscores the relevance of the findings to humans and suggests we may be able to help treat or prevent obesity by targeting the RalA pathway with new therapies," said Saltiel "We're only just beginning to understand the complex metabolism of this disease, but the future possibilities are exciting."

As with anything you read on the internet, this article should not be construed as medical advice; please talk to your doctor or primary care provider before changing your wellness routine. This article is not intended to provide a medical diagnosis, recommendation, treatment, or endorsement. These statements have not been evaluated by the Food and Drug Administration. 

Content may be edited for style and length.

References/Sources/Materials provided by:

milesmartin@ucsd.edu

https://today.ucsd.edu/story/how-obesity-dismantles-our-mitochondria

https://ucsd.edu/

http://dx.doi.org/10.1038/s42255-024-00978-0

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