White could be the new beige when it comes to fat cells, following the discovery of a switch that maintains the functions of adipose tissue in mice, transforming it from a lipid blocker to a calorie burner.
Physician-scientist Brian Feldman and molecular biologist Liang Li of the University of California, San Francisco, conducted a series of experiments on human cell cultures and mice modified with a switch for a gene that they believe regulates how we stay fat.
By depriving mice of the transcription factor Klf15, the researchers were able to shift the identity of “deep storage” white adipose tissue (WAT) to a more transient, thermoregulatory form called brown adipose tissue (BAT).
In mammals, fat tissue generally comes in two types. White fat is like a long-term savings account for calories, trapping lipids under our skin and around our soft internal organs to act as shock absorbers and insulators.
Brown fat, on the other hand, is blackened by a generous number of cellular energy generators ready to burn its fuel supply at any moment. Rare in adult humans, babies (and hibernating mammals) are fortunate to have large amounts of BAT to keep their bodies warm while they sleep.
For most of our evolutionary history, this balance between body fat and total body fat has served us well. Mature members of our species keep warm by using fat as fuel to move around, while immobile newborns benefit from a more passive form of temperature regulation.
Of course, in environments where dietary fat is abundant and mobility is limited, it is all too easy to invest a large amount of unused lipids into white fat storage, often to the increasing detriment of our health.
Nature also hasn’t made it easy to recover these fats once they’re stored, prompting researchers to look for ways to change the type of fat tissue.
“For most of us, white fat is not uncommon and we are happy to part with it,” said Feldman.
With Feldman’s previous research suggesting a role for Klf15 in fat metabolism, he decided to dig deeper and determine its specific functions.
The first big clue came from analyses comparing the amounts of Klf15 across different types of fat tissue. The transcription factor was relatively abundant in white blood cells, prompting Feldman and Li to wonder what might happen if tissues were deprived of the protein.
Know about isoproterenol stimulates brown tissues To generate heat, the pair administered doses of the compound into human WAT cultures and wild-type mice. The signs were clear that there was a relationship between brown fat activation and Klf15 levels, with a follow-up investigation revealing a adrenergic receptor called Adrb1 was the critical link.
A related receptor called Adrb3 Researchers already knew about this phenomenon, and animal studies have raised hopes that stimulating it might encourage white fat cells to change identities and become browner, making it a little easier to eliminate their reserves.
Clinical trials are exploring whether Adrb3 agonists improve metabolic health in humans, although based on findings that the receptor is not detectable in human waterFeldman is optimistic that Adrb1 could serve as a more suitable therapeutic target.
In a final test, mice modified with a kind of Klf15 gene switch increased their expression of Adrb1, making white fat tissue more “beige.”
Finding a way to generate a similar response in humans using pharmaceuticals could help overcome the barriers many people face in tapping into their fat stores, without the side effects that accompany many other approaches.
“A lot of people thought it wasn’t feasible,” said Feldman.
“We’ve shown not only that this approach works to turn these white fat cells into beige cells, but also that the bar to achieve this is not as high as we thought.”
This research was published in the Clinical Research Journal.