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Brigham Young University study: Fight fat on cellular level?

Published October 17, 2013 9:40 pm

Study • Blocking a certain lipid could prevent obesity despite a poor diet, research suggests.
This is an archived article that was published on sltrib.com in 2013, and information in the article may be outdated. It is provided only for personal research purposes and may not be reprinted.

It's a modern holy grail: A medical therapy that could let you eat anything you wanted without gaining weight.

Researchers at Brigham Young University aren't there yet, but in a new study they prevented mice from gaining weight or developing diabetes despite an unhealthy diet by blocking a certain critical lipid at the cellular level.

The lipid is called ceramide, and it's at the root of a cellular pathway that disrupts metabolism, according to BYU biologist Benjamin Bikman. For a study published recently online in Biochemical Journal, he and other researchers fed two sets of mice a high-fat, high-sugar diet for 12 weeks.

They supplemented one group's diet with myriocin, an amino acid that inhibits ceramide.

While the first set of animals gained weight and became diabetic, the myriocin group did not — despite eating the same bad diet. Researchers nicknamed them "Adonis mice," because they got bigger and more robust than normal mice.

Ceramide slows metabolism by altering the physical form of the cells' mitochondria, disrupting cells' ability to respond to insulin and take up sugar from the blood.

"If you don't have functioning mitochondria, you can't use fat for fuel," Bikman said.

It also changes how the cells can use both sugars and fats for fuel. Those changes lead to high insulin in the blood, and ultimately fat build up. And as obesity develops and worsens, ceramide production only increases, making it both a cause and a consequence.

"If we can prevent this shape-changing effect from happening in the cells by stifling the ceramide, we can prevent insulin resistance," said doctoral student and co-author Melissa Smith in a statement.

Though the concept holds promise, it's far from becoming a usable therapy in humans. In the right amount, ceramide is an essential compound for life — mice bred not to produce it can die within days. For a therapy to become useful, scientists would have to figure out the exact right amount to inhibit.

Bikman and his lab will next examine whether inhibiting ceramide also works to prevent obesity related to environmental factors, such as car exhaust.

Still, the findings could help fight obesity and Type II diabetes, possibly within the next decade.

"This by no means is the end," Bikman said. "There's still a lot more, but this is certainly giving us a direction."

lwhitehurst@sltrib.com

Twitter: @lwhitehurst