'Beige fat' and aging

New research suggests a strategy to ward off age-related weight gain, which could prevent obesity and associated health disorders like Type 2 diabetes, heart disease and chronic inflammation.

By stimulating the production of a certain type of fat cells, the effects of a slowing metabolism could be reversed, according to a new study.

Mammals, including humans, have two main types of fat: white adipose tissue (WAT), which stores energy from excess calorie intake, and brown adipose tissue (BAT), which burns calories to produce heat to maintain body temperature.

The study, published in Nature Communications, shows therapeutic promise in a third type of fat, a subtype of WAT: beige fat. Beige fat has the same cellular precursors as white fat and the same thermogenic properties as brown fat, which means it helps to reduce blood sugar and the fatty acids that cause hardening of the arteries and heart disease.

When a person experiences sustained exposure to cold temperatures, stem cells known as adipose progenitor cells form thermogenic beige fat cells within white fat. As people age, the response to that stimulus weakens, tipping the balance toward white fat production.

“There are seasonal changes in beige fat in young humans,” said the senior author, “but an older person would have to stand outside in the snow in their underwear to get those same effects.”

In earlier work, the authors observed that the aging process impairs the formation of beige fat cells in response to cold temperatures. Identify the biochemistry behind the slowdown, he said, and the same process could be reversed to achieve therapeutic outcomes.

“This is the ultimate goal,” said the lead author of the new study. “Without having to subject people to cold exposure for prolonged periods of time, are there metabolic pathways we can stimulate that could produce the same effect?”

In the paper, they reveal the role of a specific signaling pathway that suppresses beige fat formation in older mice by antagonizing the immune system. By suppressing that pathway in aging mice, the scientists were able to prompt beige fat production in animals that otherwise formed only in WAT.

The researchers 
show that ageing beige adipocyte progenitor cells (APCs) overexpress platelet derived growth factor receptor beta (Pdgfrβ) to prevent beige adipogenesis. They  show that genetically deleting Pdgfrβ, in adult male mice, restores beige adipocyte generation whereas activating Pdgfrβ in juvenile mice blocks beige fat formation.

Mechanistically, the authors find that Stat1 phosphorylation mediates Pdgfrβ beige APC signaling to suppress 
IL-33 induction, which dampens immunological genes such as IL-13 and IL-5. Moreover, pharmacologically targeting Pdgfrβ signaling restores beige adipocyte development by rejuvenating the immunological niche.