Linked to serious health problems including cancer, diabetes and cardiovascular disease, obesity affects more than a third of adults in the United States. Presently, there are few safe and effective nonsurgical therapeutic interventions available to patients with obesity.
Now, a multi-disciplinary team of researchers has demonstrated that a metabolic regulatory molecule called Them1 prevents fat burning in cells by blocking access to their fuel source. Led by microscopy experts, the study may contribute to the development of a new type of obesity treatment. The team’s findings were published in Nature Communications.
To help explain how the protein Them1 turns off heat production, the authors used light and electron microscopy to observe Them1 in action in mouse brown fat cells grown in the laboratory.
“Them1 is an interesting molecule,” said the senior author. “If you inhibit or block its expression, metabolism increases and that reduces body weight.”
The experiments showed that when the cells are stimulated to burn fat, a chemical modification causes Them1 molecules to spread out, or diffuse, throughout the cell. This frees the cellular powerhouses called mitochondria to efficiently turn the cell’s fat stores into energy. But when the stimulation stops, Them1 molecules quickly reorganize into a structure called a biomolecular condensate. Situated between the mitochondria and the fats they use as fuel, the condensed Them1 molecules limit energy production.
“It turned out to be so incredibly interesting,” said the author. “We asked other microscopy experts whether they had ever seen anything like the unusual images we found in resting cells. Using very sophisticated electron microscopy techniques, we were able to show — for the first time, as far as we know — what the bimolecular condensate looks like in electron microscopy.”
“The study explains a new mechanism that regulates metabolism,” said the author. “Them1 hacks the energy pipeline and cuts off the fuel supply to the energy-burning mitochondria. Humans also have brown fat and produce more Them1 in cold conditions, so the findings may have exciting implications for the treatment of obesity.”
https://www.nature.com/articles/s41467-021-23595-x
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fthioesterase&filter=22
Molecular switch that regulates fat burning in mice
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