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Stanford University School of Medicine

Secrets of fat cells discovered

Why aren’t we all drowning in fat? Before talking with Mary Teruel, PhD, this question certainly never occurred to me. (On a personal level, though, I admit I’ve wondered about the opposite!) But after our conversation I saw why it’s such a good question — and how great it is that Teruel has come up with an answer.

Normally your body replaces about 10 percent of your fat cells a year, explained Teruel, a Stanford assistant professor of chemical and systems biology. Little by little, the old ones die, and new ones develop from flat, spindly precursor cells.

Teruel knew, based on her previous experiments, that the switch that triggers the conversion of precursor cells into fat cells is an “on-off” sort, not a dimmer which can be dialed up and down.

Here’s what’s going on in a little more detail: The switch controls the amount of PPAR-gamma in a cell. PPAR-gamma is a nuclear receptor protein that is the master regulator of fat-cell development. In precursor cells, the switch is in the “off-state” and there’s no PPAR-gamma in the cell, but when the cell senses a stimulus that can cause fat cell development, the switch flips to the “on-state” and the cell rapidly makes huge amounts of PPAR-gamma which then turns on hundreds of downstream genes that create a full-fledged fat cell over a period of up to 12 days.

So here’s what was puzzling Teruel: Every human has a large number of precursor cells that all sense the same stimulus, but rather than all converting at once to fat cells (causing us to “drown in fat”) for a given strong stimulus, only a few cells develop into fat cells at any given time, allowing a healthy, constant renewal of our fat tissue. What allows this slow, controlled renewal of fat cells, as well as prevents the unhealthy situation in which all fat cells would turn back into precursors when PPAR-gamma drops below the threshold needed to flip the switch on?
If you can manipulate the rate fat cells mature, you could do a lot for obesity.
Experiments she did with postdoctoral researcher Robert Ahrends, PhD, and colleagues, explain, and provide clues about how to control the rate at which fat forms.

The answer, they discovered, has two parts. First of all, they discovered that the master fat-regulator switch has multiple layers of feedback. Teruel, who has a PhD in aeronautical engineering, explains that these multiple layers allow the body to control the rate of fat cell formation much as a pilot would control the pitch of an aircraft. Second, they found that not all precursor cells are alike — they vary in the quantity they carry of PPAR-gamma and other regulatory proteins.

This realization is a big deal. For one thing, it gives researchers new ideas for treating obesity and diabetes — so far, conditions that resist effective treatment without serious side effects.

“If you can manipulate the rate fat cells mature, you could do a lot for obesity,” she pointed out.

“This might be the heart of how you treat disease,” said Teruel. “We can’t just use one drug for treatment. Disease is more complicated than people think. It would be like trying to control an airplane and only being able to turn the rudder. This might work in a car or boat, but an airplane can move in three-dimensions, and a change in any one dimension affects the other two. Only controlling one dimension is a sure way to crash the plane.”

Teruel’s Stanford website has more info about her research as well as a striking depiction of a fat cell’s development.

They published the results of their studies on Friday in the journal Science (subscription required). They were supported by Stanford University New Faculty Startup Funds, the National Institutes of Health (grant P50GM107615), the German Research Foundation, and the American Heart Association.

Previously: Early findings show nutrigenomics could make weight loss more efficient, Study shows banning soda purchases using food stamps would reduce obesity and type-2 diabetes, Fed Up: A documentary looks for answers about childhood obesity
Image by CNIC

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