A research team from City of Hope discovered that newly identified CP-A stem cells in the male body control fat formation starting from middle age.

The Challenge of Growing Belly Fat

Men often notice a frustrating trend as they hit their mid-40s: despite minimal changes in diet or exercise routines, their waistlines begin to expand. This phenomenon has led many to search for the best diets, exercise routines, and lifestyle changes appropriate for individuals over 40.

Unraveling the Mechanism

Researchers from City of Hope and the University of California, Los Angeles (UCLA) have recently shed light on this issue by publishing their findings in the journal Science. They discovered a previously unknown population of stem cells in white adipose tissue (WAT) that aggressively produces new fat cells as men age. Experiments with middle-aged mice revealed that over 80% of visceral fat cells were newly formed, compared to nearly none in younger mice.

Shattering Old Assumptions

This research challenges the long-standing belief that belly fat increases primarily due to the enlargement of existing fat cells. The study suggests that adipogenesis, or the formation of new fat cells from stem cells, is a significantly more impactful mechanism.

Investigating Cellular Autonomy

In an interesting twist, the researchers transplanted adipocyte progenitor cells (APCs) from older mice into younger ones. The outcome was striking: the older APCs generated an abundance of fat cells regardless of the host’s age, while younger APCs resulted in minimal fat creation in older mice. This strongly indicates that the cause lies within the cells themselves, not in their environment.

Identifying CP-A Stem Cells

Using single-cell RNA sequencing (scRNA-seq), the researchers identified a novel cell population known as “committed preadipocytes, age-enriched” or CP-As. These cells appear during middle age, peak, and then decline over time. As Dr. Qiong Wang noted, “We discovered that aging triggers the emergence of a new type of adult stem cell, promoting the massive production of new fat cells, particularly in the abdominal region.”

The Role of LIFR and Gender Differences

Significantly, the team identified the leukemia inhibitory factor receptor (LIFR) as a molecular switch that enhances fat formation in CP-As. In young mice, LIFR plays a negligible role, but it becomes essential in middle age. Notably, chronic treatment with a LIFR inhibitor successfully prevented an increase in visceral fat during experiments.

Moreover, the research revealed a stark gender disparity: significant adipogenesis predominantly occurred in male mice, while females only exhibited moderate weight gain during the same time frame. This raises concerns that middle-aged men are particularly at risk for visceral obesity and associated metabolic disorders like Type 2 diabetes and heart diseases.

Confirming Findings with Human Tissue

To solidify their findings, the team analyzed human fat tissue across various age groups using the same scRNA-seq methodology. They found a similar increase in CP-A-like cells among middle-aged individuals, confirming their strong capacity for fat cell generation.

Future Directions and Current Limitations

While the understanding of CP-As and their role in metabolic disorders offers promising avenues for new medical solutions, there are currently no approved medications targeting these cells or LIFR in humans. The researchers aim to monitor CP-A cells in further animal studies to develop strategies for potentially blocking their effects.

Until such therapies are available, traditional prevention through exercise and dietary control remains the most effective strategy to combat age-related belly fat.