As people reach middle age and beyond, their waistlines tend to expand. Additional abdominal fat is known to cause a variety of health problems; it can accelerate aging; slow metabolism down; and raise the risk of cardiovascular and metabolic diseases and other disorders. New research may have identified a cellular problem that leads to the middle-age increase in belly fat. The findings, which have been reported in Science, may have also revealed a new drug target for therapeutics that could lessen belly fat and reduce disease risk.
"People often lose muscle and gain body fat as they age, even when their body weight remains the same," said co-corresponding study author Qiong (Annabel) Wang, Ph.D., an associate professor at City of Hope National Medical Center. "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."
We carry brown or white adipose tissue, or fat. Fat cells are known to get larger as people get older, and scientists hypothesized that white adipose tissue (WAT) also starts creating more fat cells during aging.
The investigators first collected WAT stem cells called adipocyte progenitor cells (APCs), which can mature into fat cells. They were taken from young and older mice, and then transplanted into young mice. The researchers saw that young mice that received APCs from old mice started to quickly create huge numbers of fat cells. But the young mice that received APCs from young mice did not start generating fat cells.
The researchers also assessed the activity of genes in the APCs of young and older mice. This confirmed that APCs become highly active once mice get to middle age, and then start generating new fat cells.
Most adult stem cells grow less as the body gets older, but the opposite is true for APCs. They get older and start evolving and spreading, noted Adolfo Garcia-Ocana, Ph.D., chair of the Department of Molecular & Cellular Endocrinology at City of Hope, among other appointments. "This is the first evidence that our bellies expand with age due to the APCs' high output of new fat cells."
The aged APCs also became a new kind of stem cell known as committed preadipocytes, age-specific (CP-As). These appear in middle age, and begin to generate new fat cells. This can explain weight gain in older mice.
This process was driven by a biochemical pathway called leukemia inhibitory factor receptor (LIFR). Young mice can make fat without this pathway, but older mice require it, Wang explained. "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."
When the researchers analyzed human tissue from people with a range of ages, their findings were confirmed. CP-A cells were more abundant in middle aged individuals, and human CP-As can make lots of fat cells.
"Our findings highlight the importance of controlling new fat cell formation to address age-related obesity," said Wang. "Understanding the role of CP-As in metabolic disorders and how these cells emerge during aging could lead to new medical solutions for reducing belly fat and improving health and longevity."
Sources: City of Hope National Medical Center, Science
