Experts Finally Figured Out Why It’s So Common To Regain Weight. Here’s What You Can Do About It.

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Having a good memory is generally considered a useful trait, whether we’re talking about muscle memory or cognitive function. However, when it comes to weight loss, memory on a cellular level can actually work against you, playing a significant role in making it harder to maintain weight loss and easier to regain the pounds.

Even after losing weight, some people’s fat cells retain a memory of obesity, recent research suggests—and that could be why many individuals find it tough to keep weight off long-term.

Researchers obtained fat biopsies from people at a healthy weight and from people with obesity before and after two years of weight loss for the study, which was published in the journal Nature in November 2024. Then, they performed an RNA analysis on the samples. The cells from the people with obesity had similar changes at the start and end of the study, even after they were no longer considered obese.

They also studied the fat cells of mice: “We showed that fat cells from [formerly] obese mice are [functionally] different and re-gain weight faster [than mice who were always at a healthy weight],” says Ferdinand von Meyenn, PhD, study author and assistant professor at the Department of Health Sciences and Technology at ETH Zurich in Switzerland. “This indicates there is a cellular memory that works against weight loss.”

Meet the experts: Ferdinand von Meyenn, PhD, is an assistant professor at the Department of Health Sciences and Technology at ETH Zurich in Switzerland. Dina Peralta-Reich, MD, is an obesity medicine specialist and founder of New York Weight Wellness Medicine.

While this does not mean that it’s impossible to keep the weight off after you’ve lost, doctors agree that this finding tracks with what they see occur with many patients.

“I don’t find [this research] surprising,” says Dina Peralta-Reich, MD, an obesity medicine specialist and founder of New York Weight Wellness Medicine. “In the clinical world, we do tend to see patients that, after having either bariatric surgery or significant weight loss with weight loss medications, they’re maintaining lifestyle modifications, [but] tend to start increasing weight after a certain period of time. So that does indicate that there might be some obesogenic memory in the patients.” Although, Dr. Peralta-Reich emphasizes that this is just one study and more research is needed.

In the future, von Meyenn says, there could be novel drugs or other methods (including specific diets or dietary compounds) to help rewire the epigenome (essentially the chemical compounds that tell the genome—your DNA—what to do) so that the obesity genes become inactive. “We find that during obesity, some long-term epigenetic changes occur, and if we could restore the non-obese state (i.e. target these epigenetic changes), we might be able to also erase the obesogenic cellular memory,” von Meyenn says. “That should normalize the function of the adipose tissue back to ‘normal.’”

While these potential treatments are only in the early stages of research—and von Meyenn emphasizes that prevention of obesity in the first place is ideal—there are a few things you can do now to prevent weight regain. Ahead, Dr. Peralta-Reich, shares her tips.

The 3 Most Important Diet And Workout Habits To Practice To Avoid Weight Regain

1. Consider an anti-inflammatory approach to your nutrition.

“Nutrition is huge, and it’s very individualized because it depends on the person’s age, physical activity, and metabolism,” says Dr. Peralta-Reich. In general, you want to maintain a balanced diet with an emphasis on protein and vegetables, and avoid refined carbs and overeating.

“Age also plays a huge factor because the metabolism of a 30-year-old versus the metabolism of a woman that is [in] perimenopause and menopause is very different,” she notes. “During perimenopause [and] menopause, you have a decrease of estrogen in your body, and we know when this decrease of estrogen happens, fat accumulation goes up and muscle mass goes down,” she says.

Because of this, Dr. Peralta-Reich recommends an anti-inflammatory diet. Reducing inflammation can help support healthy estrogen levels and overall hormonal balance and function.

2. Avoid fad diets and alcohol.

Just as important as what you do is what you avoid: Fad diets, including most types of fasting, just contribute to the “yo-yo” effect of weight loss and gain, Dr. Peralta-Reich says. “Most fat diets are not healthy because when you have a rapid weight loss, you’re losing muscle mass instead of fat,” she emphasizes.

She also recommends avoiding or cutting back on alcohol: “It interferes with your metabolic health and increases your body fat percentage and visceral fat,” she says. Additionally, as you age, your body metabolizes alcohol differently, so you may feel worse after a night of drinking during peri and menopause than you did when you were younger. “Nothing good comes from alcohol,” Dr. Peralta-Reich says.

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3. Increase and maintain muscle with weight lifting.

“We know that [weight training is] key for maintaining good muscle mass and keeping the fat percentage down,” says Dr. Peralta-Reich, who adds that a moderate amount of cardio is still important for cardiovascular health. Strength training two to three days per week is one of the best ways to prevent muscle loss and preserve the muscle you do have, whether you’re in the weight loss or maintenance phase.

How To Know If A Convo With Your Doctor About Weight Loss Medications Makes Sense For You

Dr. Peralta-Reich underscores that there’s a difference between someone who was slightly overweight and lost 20 pounds, versus someone who was truly obese in terms of weight regain.

“A patient with obesity that has struggled [their] whole life to be able to lose weight and wasn’t able to do it just with lifestyle modifications, then that [person] needs to be on the [weight loss] medication,” she says. “Chances are that this person has to stay on the medication, not necessarily at higher dose, but on maintenance dose, for a long period of time or their life.”

Similarly, people who have had bariatric surgery are often good candidates to be on GLP-1s as maintenance after surgery to prevent that yo-yo effect, she says. “Without the medication, it’s very difficult for patients sometimes to maintain the weight,” Dr. Peralta-Reich says.

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