New study explains why people gain stubborn belly fat in middle age

Keeping weight off during middle age is not easy. As the years pass, many people—especially men—find themselves gaining stubborn belly fat. Now, researchers have uncovered key reasons why this happens, offering hope for new ways to combat age-related weight gain and metabolic diseases.

In new research published in Science, scientists at City of Hope and UCLA revealed that aging triggers a hidden switch in your body’s fat-making system. Qiong (Annabel) Wang, Ph.D., an associate professor at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute, explained that aging awakens a new type of adult stem cell that fuels fat production around your abdomen.

“People often lose muscle and gain body fat as they age—even when their body weight remains the same,” Wang said. Her team focused on white adipose tissue, or WAT, the primary kind of fat tissue that grows with age.

The research team suspected that more was happening than just the enlargement of existing fat cells. They proposed that the body might be creating an entirely new batch of fat cells as you age, especially around the belly.

To test this, Wang and her colleagues transplanted adipocyte progenitor cells, or APCs, from both young and middle-aged mice into young mice. They observed that APCs from older mice quickly produced a flood of new fat cells, while APCs from young mice barely generated any new cells even when placed into older bodies. This proved that aging, not environment, unlocked a powerful ability in these cells to make fat.

Using single-cell RNA sequencing, the team closely studied the behavior of these APCs. They discovered that while APCs stayed mostly dormant in young mice, they became highly active during middle age. They produced many new fat cells, particularly around the midsection.

Even more surprising, the researchers found that aging transformed APCs into a new type of stem cell they named committed preadipocytes, age-specific (CP-As). These CP-As multiplied rapidly and had a strong ability to generate new fat cells.

Adolfo Garcia-Ocana, Ph.D., chair of the Department of Molecular & Cellular Endocrinology at City of Hope, pointed out the significance of this discovery: “While most adult stem cells’ capacity to grow wanes with age, the opposite holds true with APCs—aging unlocks these cells’ power to evolve and spread. This is the first evidence that our bellies expand with age due to the APCs’ high output of new fat cells.”

The team's research showed that CP-As arise specifically during middle age and continue fueling fat buildup through early aging, providing new insights into why visceral fat is so difficult to control after your forties.

The scientists then identified a key signaling pathway that made this fat-boosting process possible. A protein receptor called the leukemia inhibitory factor receptor (LIFR) was found to be critical in promoting the CP-A cells’ ability to multiply and form new fat.

“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,” Wang explained. Without LIFR, CP-As could not generate fat as aggressively.

This finding opens exciting possibilities for medical interventions. Targeting the LIFR pathway could eventually help prevent or slow down belly fat accumulation in middle-aged and older adults.

To confirm their results applied to humans, the researchers studied APCs from people of different ages. Single-cell RNA sequencing revealed similar CP-A cells appearing in middle-aged individuals, just like in mice. These human CP-As also showed strong fat-producing abilities, suggesting that similar biological mechanisms drive age-related weight gain across species.

Belly fat is more than a cosmetic issue. It increases the risk for a host of serious conditions, including insulin resistance, heart disease, and other metabolic disorders. Even if your body mass index stays the same, a rise in visceral fat during middle age can shorten your healthy lifespan.

Previous research has shown that WAT plays a vital role in regulating hormones and metabolism. It has great plasticity, meaning it can change composition and behavior based on your body’s needs. As energy expenditure slows with age and tissues change, WAT undergoes remodeling, adding to health problems.

Until now, it remained unclear how much of middle-age fat gain was due to simply enlarging existing fat cells versus creating new ones. Earlier work suggested that new fat cell formation, known as adipogenesis, slowed with age. But Wang’s study overturned this belief, showing that, at least in visceral fat, adipogenesis actually ramps up during middle age because of CP-As.

The study also explained why older adults can experience sarcopenic obesity—gaining fat while losing muscle—even if their overall weight does not change much.

Future research will now focus on tracking CP-A cells more closely in living animals and in human tissues. Scientists also aim to explore treatments that could eliminate or suppress these cells. Blocking CP-A formation or the LIFR signaling pathway might one day help middle-aged people maintain leaner bodies and enjoy longer, healthier lives.

"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."

The first authors of the study, Guan Wang, Ph.D. from City of Hope and Gaoyan Li, Ph.D. from UCLA, played major roles in driving this research forward.

With continued study, the mysteries behind belly fat and aging are becoming clearer. And with that understanding comes new hope for healthier, more vibrant years ahead.

Note: The article above provided above by The Brighter Side of News.

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