A study at the University of California, Irvine (UCI) has discovered a specific molecule that could treat obesity by targeting mitochondria. The findings, published in the journal EMBO Molecular Medicine, represent a new pharmacological approach to alleviate the mitochondrial fission associated with diet-induced obesity.
A high-fat diet can lead to obesity and metabolic disorders such as diabetes and fatty liver disease. Palmitic acid, a fat found in many Western diets, causes this metabolic dysfunction through mitochondrial fission in cells.
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Mitochondria play an important role in cellular energy production, but they also regulate the cell’s response to stress. Excessive mitochondrial fission impairs mitochondrial function, leading to poor metabolism and increased toxic by-products associated with insulin resistance in certain tissue types.
Overcoming obesity by restoring mitochondrial function
Previous genetic studies in mice have shown that maintaining a ‘healthy’ mitochondrial function can help overcome obesity caused by a high-fat diet.
This study showed that a small molecule that simultaneously reshapes mitochondria in multiple tissues can also reverse obesity and correct metabolic disorders, even when mice are still on an unhealthy diet. The study’s lead author, Professor Aimee Edinger (Developmental and Cell Biology), has proposed a compound that can restore mitochondrial function.
SH-BC-893, a patented synthetic, water-soluble, oral sphingolipid, can inhibit proteins involved in mitochondrial breakdown. This has been demonstrated in vitro and in vivo in mice fed a high-fat diet. SH-BC-893 inhibits mitochondrial dysfunction in the liver, brain, and adipose tissue of mice fed a Western diet.
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SH-BC-893 can also normalize the levels of the important metabolic hormones leptin and adiponectin, leading to weight loss, improved glycemic control, and recovery of hepatic steatosis after a high-fat diet.
Also helps reduce the difficulty of losing weight. Too much leptin increases appetite, while too little adiponectin is associated with a number of metabolic disorders. “The role of mitochondria is not yet well understood, but it appears that they play an important role in the link between these hormones and obesity,” said Elizabeth Serwan, one of the study’s co-authors and a researcher in the Department of Developmental and Cell Biology at UCI.
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SH-BC-893 holds promise for treating obesity through diet; SH-BC-893 has already demonstrated its safety and efficacy in animals, so future clinical trials should confirm its ability to do so in humans.
The compound has a novel mechanism of action, and if it proves safe and effective in humans, it could be a new weight loss strategy that could be used in combination with other obesity treatments.
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