Why do fat cells get fat? New suspect ID'd

ANN ARBOR, Michigan — As the world fights obesity at the human level, scientists at the University of Michigan and their colleagues have made a surprising finding at the microscopic level that could help fuel that fight.

Their work helps explain why fat-storing cells get fatter, and burn fat slower, as obesity sets in. If their findings from mice can be shown to apply to humans, they may provide a new target for obesity-fighting drugs.

By studying the tiny signals that fat-storing cells send to one another, the team has shown a crucial and previously unknown role for a molecule called Sfrp5.

The results, which appear online today and will be in the July issue of the Journal of Clinical Investigation, surprised them.

In a series of experiments, the team showed that Sfrp5 influences a signaling pathway known as WNT to stimulate fat cells – called adipocytes – to grow larger and to suppress the rate at which fat is burned in the mitochondria inside them.

By stopping cells from making Sfrp5, they were able to make mice that didn’t get as fat as quickly because their adipocytes didn’t grow large – even when the mice were fed a high-fat diet. They even showed the impact when transplanting fat from Sfrp5—deficient mice into other mice.

The research was performed with National Institutes of Health funding in the U-M Medical School laboratory of Ormond MacDougald, Ph.D., the Faulkner Professor in the Department of Molecular & Integrative Physiology, a professor of internal medicine and a member of U-M’s Brehm Center for Diabetes Research.

Working with postdoctoral fellow and first author Hiroyuki Mori, Ph.D., and colleagues, MacDougald says the team built on its previous findings about the importance of WNT signaling in fat cell development.

“WNT signaling plays a crucial role in regulating, and inhibiting, white fat cell growth and the recruitment of new cells to store fat,” he explains. “But it appears that in obesity, Sfrp5 can interfere with that signaling, and may create a feedback loop that keeps stimulating production of more of itself.”

He notes that the new results contradict previous work published by another group, which found essentially the opposite role for Sfrp5. A commentary accompanying the new U-M paper, by scientists from Denmark, notes the strong evidence behind the new findings and emphasizes the importance of further research on the topic.

MacDougald and his team zeroed in on Sfrp5 after years of studying WNT signaling between adipocytes. They and other teams had already seen that the amounts of Sfrp5 produced within fat tissue were higher in obese animals.

Air Jordan Shoes Men