NEW YORK — A team of US
researchers has uncovered the cellular culprit behind age-related abdominal
fat, providing new insights into why our midsections widen with middle age.
Published in the
journal Science, the findings suggest a novel target for future therapies to
prevent belly flab and extend our healthy lifespans.
Preclinical
research by City of Hope, one of the largest and most advanced cancer research
and treatment organisations in the US, has done this research.
“People often lose muscle and gain body fat as
they age — even when their body weight remains the same,” said Qiong (Annabel)
Wang, an associate professor of molecular and cellular endocrinology at City of
Hope’s Arthur Riggs Diabetes and Metabolism Research Institute.
“We discovered aging triggers the arrival of a
new type of adult stem cell and enhances the body’s massive production of new
fat cells, especially around the belly,” Wang added.
In collaboration
with the UCLA laboratory co-corresponding author Xia Yang, the scientists
conducted a series of mouse experiments later validated on human cells.
Wang and her
colleagues focused on white adipose tissue (WAT), the fatty tissue responsible
for age-related weight gain.
While it’s
well-known that fat cells grow larger with age, the scientists suspected that
WAT also expanded by producing new fat cells, meaning it may have an unlimited
potential to grow.
To test their
hypothesis, the researchers focused on adipocyte progenitor cells (APCs), a
group of stem cells in WAT that evolve into fat cells.
The team first
transplanted APCs from young and older mice into a second group of young mice.
The APCs from the older animals rapidly generated a colossal amount of fat
cells.
When the team
transplanted APCs from young mice into the older mice, however, the stem cells
did not manufacture many new fat cells. The results confirmed that older APCs
are equipped to independently make new fat cells, regardless of their host’s
age.
Using
single-cell RNA sequencing, the scientists next compared APC gene activity in
young and older mice. While barely active in young mice, APCs woke up with a
vengeance in middle-aged mice and began pumping out new fat cells.
A signalling
pathway called leukemia inhibitory factor receptor (LIFR) proved critical for
promoting these CP-A cells to multiply and evolve into fat cells.
“We discovered that the body’s fat-making
process is driven by LIFR. While young mice don't require this signal to make
fat, older mice do,” explained Wang. “Our research indicates that LIFR plays a
crucial role in triggering CP-As to create new fat cells and expand belly fat
in older mice.”
“Our findings highlight the importance of
controlling new fat-cell formation to address age-related obesity,” said Wang.
