Can’t keep the weight off? It could be down to your ‘fat cell memory’

If you have ditched the diet only to see the weight creep on at an alarming rate, your body may have a high metabolic set point, meaning you will always put on the pounds faster than others. Serial dieter Isabel Mohan explains what that means and how she achieved a reset

If you’re someone who’s always struggled with their weight, hearing the words “diets don’t work! You’ll put it all back on again!” can be infuriating. But in the age of Ozempic and other increasingly popular GLP-1 weight loss drugs, those newly slim people are hearing them more than ever.

New research suggests that it’s not just a case of going back to bad habits. For some people, piling weight back on is based on scientific reasoning too. If you want to be part of the estimated 15 to 20 per cent of people who do manage to keep large amounts of weight off long term, you’re going to have to work extra hard for it: studies show that “fat cell memory” can make the body nostalgic for its previous, bigger size and will do all it can to get back there – regardless of how you lost weight in the first place.

It can all feel very unfair: for an overweight person, eating more healthily is a diet by any other name, and often the very same people who shame us for being fat are the same ones poo-pooing the methods we might use to lose weight.

In the new research, published by Nature, mice who were previously obese regained weight more rapidly than those who had not been overweight. “Mice carrying this obesogenic memory show accelerated rebound weight gain,” reads the report.

“In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic ‘yo-yo’ effect often seen with dieting.”

After a lifetime of struggling to maintain my weight, it doesn’t surprise me to hear that my body might still be hankering after my long-lost size 18 maternity leggings (they were really comfy). I’m not a mouse but across my adult life, I’ve lost – and gained, and lost, and gained – a large amount of weight. In fact, if you tot up all the diets I’ve tried over the years, it adds up to about 20 stone: from losing more than five stone in six months in my late twenties via an insane 500 calories a day meal replacement plan to multiple stints at WeightWatchers and Slimming World, along with plenty of good old-fashioned calorie counting via snazzy apps like My Fitness Pal and Noom.

Sure enough, once I reached my target size and started to relax strict eating habits, my weight would often creep up again. I would try to maintain those healthy habits but pregnancy, motherhood, stress, hormones and, well, the ever-enticing lure of Tony’s Chocolonely and wine would get in the way. However, I’ve always felt a sense of unfairness: slimmer friends who seemed to live in the same way as I did always looked the same, while one heavy weekend was enough for me to go up a dress size.

Many people find themselves stuck in an endless cycle of losing weight and putting it back on (Getty)

So, how have I now managed to have joined that elite minority of people maintaining a lower weight? It hasn’t come easy. Since 2021, I’ve roughly maintained a steady weight loss of around 20kg (3 stone). Sure, my weight still goes up and down with the seasons, but in far less dramatic and dare I say more “normal” ways than in my extreme yo-yo diet days. Post-Christmas, for instance, I was about 5kg heavier than I was in spring last year when I was training for the London Marathon.

My younger self would have freaked out about this, convinced I was spiralling out of control (and then reaching for the Hobnobs to feel better about it – before signing up for Slimming World again). Now, though, I accept that my weight will always fluctuate – but these days it’s just between a size 12 and a 14, rather than a 10 and a 20. And I have triumphed over those stubborn and nostalgic fat cells of mine with regular exercise.

Mohan discovered the joys of running during lockdown (Supplied)

Yes, I’ve become that person: I exercise at least five times a week: three of those are running (I was a lockdown Couch to 5K cliche, but I have kept it up, and now I’m usually training for something), and two are strength-training, plus I average over 13,000 steps a day. This amount of exercise will sound horrifying to anyone who hasn’t got the bug – or the fat-cell memory problem. It sounded horrifying to the younger me – but now it has become a fact of my life and one that I hugely enjoy too. Finally, I can appreciate food without obsessing about it as much as I did on all those drastic measures I was resorting to before.

My eating habits have become healthier, too, of course. I don’t – can’t! – drink as much as I did in my twenties; takeaways are a monthly treat and I eat a lot of protein and fresh fruit and veg. But, for once in my life, it doesn’t feel like a diet, because I also know that it’s crucial to not be restrictive when I’m doing lots of exercise.

Frustratingly, the bleats of “eat less and move more” from people who’ve never been overweight do ring true, but I know that it takes a huge mental shift to get there. One thing that many users of Ozempic and other GLP-1 drugs mention is how the drugs remove the “food noise” and give them a portal into the minds of people who have never struggled with their weight.

‘Fat cell memory’ could be causing havoc even for the most disciplined among us (Getty)

The buzz I get from running has a similar impact on me – along with accepting that while I’ll probably never technically be slim (my BMI is still in the overweight range), I can be strong, fit and energetic.

If people who have lost a lot of weight via Ozempic or other extreme measures don’t see daily exercise in their future, the thinking is that they might now need to stay on the drug for life to stay in their size 10 jeans. Or are there other ways they can somehow “reset” their bodies and wipe that fat cell memory once and for all?

GP and Wellgood Wellbeing founder Dr Zoe Watson says she encounters a lot of patients with this exact concern. “Certainly we have known for a long time that epigenetics play a huge part in obesity,” she says. “Some people seem to be ‘genetically blessed’ to maintain the same weight their whole lives, while others struggle in a seemingly endless cycle of losing and gaining weight throughout their lives.

“For a long time, this has been explained as the body having a ‘metabolic set point’ – such that every time weight is gained and then lost – the body will do everything it can to get back to that previous higher weight.”

Dr Watson believes that adjusting our mindsets can certainly help. “The crux of the issue is that obesity and being overweight are chronic diseases,” she says. “And much like every other chronic disease we manage in general practice – asthma, diabetes, hypertension, for example – the treatment for that is lifelong.”

Mohan taking part in the London Marathon (Supplied)

This means that gaining weight after treating weight loss, whether that loss came via Ozempic, Mounjaro, bariatric surgery or simply calorie deficit, is pretty likely for many people – but that doesn’t mean you should give up; especially, if you believe that you would feel happier and healthier at a lower weight.

“Long term it is going to be about looking at lifestyle stuff to try and maintain the weight loss,” says Dr Watson. “But achieving large amounts of weight loss in the first instance through diet and exercise alone is really hard and often fails.”

So, if you are thinking about going the weight-loss drug route, Dr Watson says that addressing lifestyle factors while using a weight-loss drug will help. Instead of relying on your appetite receptors being turned off and then panicking about it afterwards, use the rapid weight loss and all that comes with it, from new clothes to increased energy, as a motivation to maintain healthy habits.

“There is also some evidence that once you have managed to maintain some amount of weight loss from your previous baseline that your metabolic set point does reset again,” she says. “It’s a hugely exciting and evolving area of research and GLP-1 drugs are one of the most exciting pharmacological treatments we’ve seen for obesity.”

While maintaining a healthier size might be harder for some of us than others, it doesn’t mean that losing weight is a big, fat waste of time. Ultimately, though, you just might have to choose between lining the pockets of the pharmaceutical companies without really knowing what the long-term health impact of these drugs might be, or lining the pockets of Sweaty Betty and Adidas.