New Research Suggests Fat Cells May Help Explain Why Diets and Weight-Loss Drugs Often Fall Short

New epigenetic research suggests one reason many diets and weight-loss drugs do not work long term may be that fat cells keep a memory of obesity, even after a person loses weight.

In a recent mouse experiment, researchers examined a chemical process in fat cells in which the hunger-related hormone asprosin triggers changes in DNA and appears to create a kind of “biological memory” inside the cell, the Washington Post reported.

Drugs such as Ozempic have become widely used in the United States for their dramatic effects, and recent polling has pointed to a decline in obesity rates. A Gallup poll released in July found that 11% of U.S. adults use GLP-1 medications for weight-loss purposes, up from 3% in 2024.

Still, many users say the benefits fade soon after they reduce or stop the medication, according to research published in JAMA Internal Medicine.

One study published in JAMA found that 83% of users who lost weight with tirzepatide regained at least 25% of their original weight loss within a year of stopping the drug.

The notion that cells preserve an obese-state “status quo” could help explain this regain. Researchers say changing the cell’s chemical makeup to switch certain functions on and off may eventually lead to better obesity treatments. (RELATED: The Real Reasons Why You Keep Paying More For Employer Healthcare)

“If we understand where that memory is coming from, maybe eventually we’ll have some way to stop that,” Seth Field, a professor of medicine in endocrinology at Case Western Reserve University and one of the study’s authors, told the Washington Post.

A separate Mayo Clinic study found that roughly one in four participants produced lower levels of GLP-1 and other hormones that help people feel full after eating.

“Obesity is a complex disease driven by different biological mechanisms,” said senior author Andres Acosta, M.D., Ph.D., a gastroenterologist and director of an Obesity Research program at Mayo Clinic in Minnesota. “Our findings suggest we can begin identifying which patients are most likely to respond to specific therapies rather than treating obesity as a single disease.”

The Trump administration’s pharmaceutical program, TrumpRx.gov, also offered “massive discounts on popular medications used to treat obesity and infertility,” including GLP-1s, a White House official told the Daily Caller News Foundation.

“Senior citizens without access to GLP-1 coverage to treat obesity gained access for just $50 per month,” the official said. “In the two months since the launch of this program, 600,000 seniors have saved a total of $216 million dollars on these life-changing medicines.”

Even with the popularity of GLP-1 drugs as a quick-fix option, they have also helped push healthcare costs higher, previous DCNF reporting found. Several U.S. small-business insurers have stopped covering the drugs because of growing use and high prices.

“The main reason for rising health insurance costs is simply that ‘healthcare’ includes more and more things every year,” Chris Pope of the Manhattan Institute told the DCNF.

“This is most obvious in the case of drugs, such as Ozempic, which didn’t even exist a few years ago,” Pope said. “They cost thousands of dollars per course of treatment, and millions of patients are now using them. Insurers often pick up most of this cost. A similar dynamic exists with new hospital services: whenever a hospital upgrades its equipment, opens a new building, or deploys a new surgical procedure which previously didn’t exist, spending on hospital care increases enormously.”