How Obesity Dismantles Our Mitochondria

In a new study researchers found that when mice were fed a high-fat diet, mitochondria within their fat cells broke apart into smaller mitochondria with reduced capacity for burning fat.

Further, they discovered that this process is controlled by a single gene.

By deleting this gene from the mice, they were able to protect them from excess weight gain, even when they ate the same high-fat diet as other mice.

Obesity occurs when the body accumulates too much fat, which is primarily stored in adipose tissue.

Adipose tissue  has important metabolic functions, such as releasing hormones and other cellular signaling molecules that instruct other tissues to burn or store energy.

In the case of caloric imbalances like obesity, the ability of fat cells to burn energy starts to fail, which is one reason why it can be difficult for people with obesity to lose weight.

How these metabolic abnormalities start is among the biggest mysteries surrounding obesity.

To answer this question, the researchers fed mice a high-fat diet and measured the impact of this diet on their fat cells’ mitochondria, structures within cells that help burn fat.

They discovered an unusual phenomenon. After consuming a high-fat diet, mitochondria in parts of the mice’s adipose tissue underwent fragmentation, splitting into many smaller, ineffective mitochondria that burned less fat.

In addition to discovering this metabolic effect, they also discovered that it is driven by the activity of a single molecule, called RaIA.

RaIA has many functions, including helping break down mitochondria when they malfunction.

The new research suggests that when this molecule is overactive, it interferes with the normal functioning of mitochondria, triggering the metabolic issues associated with obesity.

“In essence, chronic activation of RaIA 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.”

By deleting the gene associated with RaIA, the researchers were able to protect the mice against diet-induced weight gain.

Sources:

Wenmin Xia, Preethi Veeragandham, Yu Cao, Yayun Xu, Torrey E. Rhyne, Jiaxin Qian, Chao-Wei Hung, Peng Zhao, Ying Jones, Hui Gao, Christopher Liddle, Ruth T. Yu, Michael Downes, Ronald M. Evans, Mikael Rydén, Martin Wabitsch, Zichen Wang, Hiroyuki Hakozaki, Johannes Schöneberg, Shannon M. Reilly, Jianfeng Huang, Alan R. Saltiel. Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation. Nature Metabolism, 2024; DOI: 10.1038/s42255-024-00978-0

Materials provided by University of California – San Diego. Original written by Miles Martin. Note: Content may be edited for style and length.

University of California – San Diego. “How obesity dismantles our mitochondria.” ScienceDaily. ScienceDaily, 29 January 2024. <www.sciencedaily.com/releases/2024/01/240129122402.htm>.

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