New hormone helps explain how high-fat diets make us fatter

When I first took high-school biology in the early 1990s, I learned a very simplistic view of fat cells: They were, my teachers said, passive bags of calories. Fat cells stored extra energy and that was it.

But over the last two decades, that view has been upended. Starting with the discovery of leptin in 1995, researchers have found several fat-cell hormones, which we now know send complex messages around the body. Fat cells don’t just act as passive energy storehouses; they talk back.

Today, a paper in Science Signaling adds a new fat-produced hormone to the list: Adamts1 is a protein hormone made by mature fat cells that toggles the “maturation” switch on nearby stem cells. Previous researchers had discovered Adamsts1, but no one knew how it affected fat.

Now, a Stanford team has figured out that Adamts1 signals when the body needs more fat stores, telling the stem cells to differentiate into more mature fat cells. Interestingly, it sends its message (which takes the form of a drop in hormone levels) in response to two external signals that we already knew could make people fatter: eating a high-fat diet and taking glucocorticoid medications. Senior author Brian Feldman, MD, PhD, assistant professor of pediatrics, explains in our press release:

“Intuitively, people understand that when you eat more, you get fatter… You’re ingesting food, and some signal has to tell your body to make more fat. We didn’t know what was gating or triggering that process in vivo. This new research goes a long way to fill in the in-between steps.”

Feldman and his team conducted a series of experiments in cells, mice and humans to figure out how Adamts1 works. Mature fat cells usually make some of the protein. When someone eats a high-fat diet or takes glucocorticoids, the level of Adamts1 drops. This change tells stem cells in the same adipose depot to differentiate.

The big question, of course, is how this new knowledge might be harnessed to improve obesity treatments. Again, here’s Feldman from the press release:

“That won’t be a simple answer… If you block fat formation, extra calories have to go somewhere in the body, and sending them somewhere else outside fat cells could be more detrimental to metabolism. We know from other researchers’ work that liver and muscle are both bad places to store fat, for example. We do think there are going to be opportunities for new treatments based on our discoveries, but not by simply blocking fat formation alone.”

Science Signaling produced a podcast with Feldman that gives a more detailed explanation of the new discovery.

Photo by Steven Depolo