The weight loss paradox: why doing everything right still isn’t enough

For years, Kirsi Pietiläinen kept a research paper tucked away in her desk drawer.

Not because the data were flawed – they were meticulously verified. But the findings challenged one of medicine’s most enduring beliefs: that losing weight through diet and exercise always leads to better health.

“The results ran against everything we expected,” she recalls. “They didn’t align with conventional thinking – or with decades of metabolic research.”

Her team had found that after weight loss through diet and exercise, mitochondria – the energy engines inside fat cells – became less active. Instead of ramping up, as expected, the cells powered down.

“These engines convert food into energy,” she explains. “When they slow down, the body burns fewer calories, making further weight loss harder.”

It defied logic, yet the evidence was clear.

Kirsi’s dilemma wasn’t the science but the implications.

“When people ask why I waited to publish,” she says, “it’s because I didn’t know how to tell this story. It felt… dangerous.”

The data showed that while diet and exercise reduced mitochondrial activity in fat cells, bariatric surgery boosted it and restored energy production.

“We’ve told patients weight loss is the goal,” she says. “But what if the body doesn’t always agree?”

When weight loss stops working

That question – the tension between what we see and what the body does – stayed with her. Eventually, it pushed her to do what all scientists must: face the contradiction.

And in doing so, it led her somewhere unexpected – not just into the biology of obesity, but into the deeper systems that shape how we treat it, talk about it, and understand it.

Kirsi Pietiläinen’s research challenged the long-held belief that weight loss always improves internal health. Her team found that in people with obesity, mitochondrial activity in fat tissue was already low – and dropped even further after dieting.

Sometimes weight loss resets the body. Sometimes, it doesn’t touch the deeper systems at all. And sometimes, the body simply resists – even when we do everything right.

That dissonance – between shrinking waistlines and stalling biology – refused to stay quiet. And it became the starting point for everything that followed. To understand what the body was doing, Kirsi had to go back – to the beginning.

Moving beyond blame

When Kirsi Pietiläinen began her medical training in the 1990s, she thought she understood obesity.

“We were taught a simple equation,” she says. “Calories in, calories out. Eat less, move more. That should work.”

But in the clinic, reality told a different story.

“From the beginning, I realised obesity isn’t about choice,” she says. “There’s so much more going on – your appetite, your internal controls, your hormones. But we didn’t yet have the science to explain it.”

Patients described doing everything right. They exercised, tracked calories, followed the rules. Some lost weight – but it came back. Many felt constantly hungry. Others ate well but still gained weight.

“The advice was always, ‘Try harder,’” Kirsi recalls. “But that just made people feel like they were failing.”

A relief to be believed

The more patients she listened to, the clearer it became: this wasn’t about willpower. Obesity was a chronic, biologically rooted condition – and the medical system had been blaming the wrong thing.

Kirsi had grown up in that same culture. Shifting her own mindset wasn’t easy. But her patients kept teaching her. And she started to listen.

Those stories stayed with her – and eventually began to shape how she approached science itself.

One woman described her frustration during a consultation. She walked every day, ate healthily, followed every recommendation. Still, the hunger didn’t go away.

“They can, of course, decide what they eat,” Kirsi says, “but they can’t decide whether they became satiated or not.”

When she explains that biology – not willpower – is the issue, something shifts.

“It’s a big relief for me,” one patient said, “not needing to think that I was doing something wrong.”

Twins can teach us about weight

Those moments – where lived experience meets science – are what first led Kirsi to look deeper.

It began with a casual conversation in a car. Kirsi Pietiläinen and her mentor, Professor Aila Rissanen, were discussing the stubborn mystery of obesity when Aila suggested something simple:

“Why don’t we study twins?”

For Kirsi, it was a turning point.

“Twins are a perfect natural experiment,” she says. “They share the same genes, but sometimes live very different lives. That makes them incredibly powerful for understanding what shapes weight.”

She began working with Jaakko Kaprio, who managed Finland’s twin cohort – one of the most comprehensive in the world.

At first, the results confirmed what textbooks had long said: genetics play a major role. Most identical twins showed similar weight patterns across their lives.

But the real insights came from the mismatches – identical twins where one sibling developed obesity and the other didn’t.

“Those were the goldmines,” Kirsi says. “They showed us something else was at play – something environmental, or biological, or both.”

Her team dug deeper: collecting fat tissue, analysing hormones, mapping molecular patterns. And the more they looked, the more surprising the story became.

“We weren’t just asking why people gained weight,” she says. “We were asking what their bodies were doing in response to it.”

One signal stood out: mitochondria – the tiny engines inside fat cells.

“We saw that in people with obesity, the mitochondria were underactive,” Kirsi says. “That wasn’t the shocking part. What surprised us was that after dieting, the activity went down even more.”

When the body pushes back

The findings ran counter to every public health message of the past 50 years.

“We were afraid to publish it,” Kirsi admits. “It upended our assumptions about how metabolism responds. How could we tell people that doing the right thing might actually slow their metabolism further?”

Eventually, they did publish. And as the research continued, they noticed something even more surprising: Through a collaboration with Anne Juuti, head of bariatric surgery at Helsinki University Hospital, they discovered that patients who lost weight through surgery showed the opposite effect: their mitochondria didn’t become less active – they became more active. Their mitochondrial activity didn’t drop – it improved.

“That was the moment I realised that we’d been lumping all weight loss together,” Kirsi says. “But the body responds differently depending on how it happens. That changes everything.”

The twin studies hadn’t just revealed how much genetics matter. They showed something else: the body’s fierce ability to defend its weight – even against strict diets or lifestyle change.

And that shifted the question entirely.

“It wasn’t just ‘How can people lose weight?’ anymore,” she says. “It was: ‘What is the body trying to protect? And how can we work with that biology instead of fighting it?’”

For clinicians, the implications are clear. Weight-loss advice shouldn’t be one-size-fits-all. It needs to reflect how each body responds – biologically, not just behaviourally.

Fat cells shut down the burn

For years, Kirsi Pietiläinen held on to a finding that challenged everything she’d been taught: after people lost weight through diet and exercise, the mitochondria in their fat cells – the tiny engines that convert food into energy – became less active.

That slowdown made it harder for the body to burn calories, complicating further weight loss. That was the paradox. Weight loss usually improves blood glucose and cardiovascular health. But on a cellular level, at least in fat, the body seemed to resist.

Her team began comparing different forms of weight loss – and found something striking: not all weight loss is created equal. The body’s response depended on how the change was triggered, and what biological signals it set in motion.

When the body has other plans

In fat tissue, mitochondria do more than generate energy. They help decide whether the body stores calories or burns them. When they slow down, the body becomes more inclined to hold onto fat – even during weight loss.

And that’s the contradiction. Weight loss often improves blood glucose and heart health. But Kirsi’s research suggests those surface-level wins may not reflect what’s happening deeper inside the body.

“I thought – how can I tell patients this?” she says. “We’ve told them weight loss is the goal. But what if the body doesn’t always agree?”

That tension – between what we see and what the body does – stayed with her. And eventually, it forced her to do what all scientists must: face the contradiction.

That question would take her beyond biology – into the systems that shape how obesity is treated, misunderstood, and judged.

But first, she had to understand one thing: what were these mitochondria actually doing? And why would they turn down the burn?

The shutdown inside fat cells

For decades, fat was seen as inert – a warehouse for excess calories. A passive depot for storage, not decision-making.

Kirsi wasn’t convinced.

“We always talked about fat as lazy – saw it as passive rather than perceptive,” she says. “But it didn’t make sense. I believed adipose tissue was doing more than we realised.”

So her team started digging deeper, using advanced “omics” tools – like genomics and other methods that capture broad patterns of cellular activity, almost like molecular fingerprints. These techniques allowed them to map thousands of biological signals inside fat tissue.

What they found rewrote the rules.

“In obesity, the energy producers in fat cells weren’t just underperforming,” Kirsi says. “They seemed to be intentionally turned down.”

The survival switch

These cellular engines don’t just turn food into fuel. In fat, they help decide whether energy gets burned or stored.

“But in people with obesity,” Kirsi says, “the cell’s energy systems resisted releasing stored fuel. They were acting like the body was under threat – like it needed to protect its fat stores.”

That idea was radical.

“Adipose tissue is anything but inert,” she says. “It’s responsive, strategic, deeply involved in energy balance. Its mitochondria might be part of how the body defends a higher weight.”

To Kirsi, it no longer looked like failure. It looked like the body flipping a survival switch.

And that changed everything – how she understood obesity, how she talked to patients, and how she thought the medical system needed to respond.

This reframe could transform care. Instead of treating resistance to weight loss as non-compliance, providers might see it for what it is: the body following ancient biological programming. And that calls for new expectations – and new tools.

As her team dug deeper, the surprises kept coming. Ones that would reshape not just the science, but her worldview.

Seeing obesity more clearly

The surprises didn’t stop with mitochondria.

“We were scratching our heads,” Kirsi says. “We thought we’d see something with lipids or insulin. But instead, we saw a signal in branched-chain amino acid metabolism. That wasn’t even on our radar for fat tissue.”

Branched-chain amino acids – often linked to muscle recovery – turned out to behave differently in fat. Their processing was disrupted, hinting at unexpected roles in energy storage and metabolism.

“In people with obesity, this pathway in fat cells looked disrupted,” she says. “It was a hint – maybe fat tissue is responding to something deeper. That’s when everything shifted for me. Fat isn’t just storage. It’s a decision-maker. It senses. It responds. It adapts. It’s part of how the body tries to defend itself.”

The shift reshaped her science. What if the body isn’t broken, but overcorrecting? What if resistance is a survival system, misfiring in modern life?

These questions didn’t make things simpler. But they made the research more honest – and the medicine more human.

When effort isn’t enough

Over time, Kirsi began to hear the same story again and again.

“The more you talk to people,” she says, “the more you’re interested in their stories, their lives – then you understand: there are connections. You talk to 10 people, and they tell you pretty much the same things.”

That shifted her thinking. Maybe the issue wasn’t effort – but biology. Maybe the body was holding on.

And if patients were doing everything right, but their bodies still resisted – what did that mean for how medicine should respond?

The deeper Kirsi looked, the clearer it became: weight loss isn’t a reset button.

“Weight loss isn’t inherently bad,” she says. “But it doesn’t always address what’s underneath. Sometimes, it even activates the body’s defence mechanisms.”

Our bodies evolved to survive famine, not modern diets. So when we lose weight, the body may respond as if food is scarce – by clinging to fat, not letting it go.

That survival reflex, once essential, now works against us. Even with discipline and care, the body may resist – to protect what it thinks we still need.

The chemistry of hunger

For decades, the message was simple: if people just tried harder, they’d succeed.

But Kirsi’s data told a different story.

“The body doesn’t always want to let go,” she says. “Sometimes, it fights back.”

That insight forced a new question – not why people struggle to lose weight, but what the body is trying to do when we ask it to change?

“It wasn’t about failure,” she says. “It was about function. The body was doing something. I just didn’t know what.”

That shift deepened as she began listening more closely to the people inside those bodies.

And what she found was that resistance didn’t stop at fat cells. It reached higher – into the brain, and into the chemistry of hunger itself.

Why fullness doesn’t always feel full

If mitochondria explained why fat was hard to lose, hormones explained why many people never felt full to begin with.

“I kept hearing the same thing from patients,” Kirsi says. “‘I’m always hungry.’ And this wasn’t emotional eating – it was physical, gnawing hunger that wouldn’t go away.”

So her team started measuring the chemical messengers that tell the brain it’s time to stop eating – hormones like GLP-1, PYY, and others involved in satiety. These first measurements, done in collaboration with hormone pioneer Jens Juul Holst, revealed something striking.

“These hormones act like internal stop signs,” she explains. “But in people with obesity, they’re often too low. So even after eating enough, the brain doesn’t get the message.”

That’s why hunger lingers – not from lack of discipline, but from missing signals.

“Their biology plays a larger role than choice ever could,” she says. “And we’d been ignoring that.”

The woman who never felt full wasn’t exaggerating. The man hungry again after 20 minutes wasn’t imagining it. Their biology was speaking – and no one had been listening.

From that point on, Kirsi stopped seeing obesity as a visible condition. She saw it as a hidden systems disorder – one medicine had misread for far too long.

And the deeper she looked, the more urgent her question became: what could reset the system?

Surgery can rewrite the rules

If dieting pushed the body into resistance mode, bariatric surgery seemed to flip the script.

Kirsi turned her attention to patients who had undergone gastric bypass  – procedures that reroute parts of the digestive system and often lead to substantial weight loss.

But she wasn’t looking at the scale. She was looking at their fat tissue.

“What we found was the opposite of what we saw with dieting,” she says. “Surgery appeared to trigger a different metabolic response – one that reactivated energy production and improved overall cell function.”

It wasn’t just about eating less. Post-surgery patients often consumed even fewer calories than dieters. The difference, she believed, was in the biological signals the surgery set in motion.

“Appetite hormones improved. Satiety signals surged. And somehow, the mitochondria responded.”

The message was clear: how weight is lost matters. Some pathways seem to trigger cooperation. Others, defence.

These findings could help guide clinical decisions. Providers may need to consider not just how much weight is lost – but how the body is asked to lose it. Each method – surgical, pharmacological, behavioural – engages biology in its own way.

And for Kirsi, a new question emerged: could medicine replicate those effects – without surgery?

Working with biology, not against it

Kirsi Pietiläinen isn’t a surgeon. But when she saw how bariatric surgery revived mitochondrial activity in fat, she had to ask: could medication do the same?

“It wasn’t the weight loss that fascinated me,” she says. “It was the biology – the hormone shift, the mitochondrial recovery.”

She turned her attention to GLP-1 receptor agonists – medications that mimic a natural gut hormone released after eating. These drugs help regulate appetite and blood glucose by signalling fullness to the brain, easing hunger without effort.

But Kirsi suspected the effects went deeper.

Her team began collecting fat biopsies from patients on the drugs and from those on placebo, looking at changes inside the cells themselves.

“We’re still investigating the exact mechanisms,” she says. “But something is clearly happening.”

“I’m a big fan of obesity medications,” she adds. “They’ve changed how we treat people – not by demanding discipline, but by working with their biology.”

And that, to her, is the future: restoring internal balance, not just shifting numbers on a scale.

But science alone wasn’t enough. People needed more than answers – they needed support.

Care that matches the science

Scientific discovery means little if it doesn’t lead to change. For Kirsi Pietiläinen, the goal has never been knowledge for its own sake – it’s been care.

“We need to turn insight into systems,” she says. “Not just study people – but support them.”

That conviction led her to help design a comprehensive digital program for people living with obesity. But it wasn’t another diet tracker. It was a long-term support system – built from the ground up to treat the whole person.

“We built it from scratch,” she explains. “That meant we could shape not just what we delivered, but how we talked about obesity – and remove the shame that too often surrounds it.”

The program offers weekly sessions on nutrition, movement, sleep, stress, and mindset. But its most radical feature wasn’t digital. It was personal.

“Every participant is paired with a professional,” Kirsi says. “Not automation. Not a chatbot. An actual human being. Because the most important part of treatment is another human.”

Today, more than 2,500 people are enrolled yearly. And what they receive isn’t a quick fix. It’s sustained support – rooted in biology, grounded in respect, and designed for real life.

When listening changes the science

The success of the program wasn’t driven by lab results alone. It was shaped by something more powerful: people’s lived experiences.

“Our patients’ stories have taught me as much as the literature,” Kirsi says. “What they’ve tried. What they’ve been through. It’s central to how we work – and why.”

One story stands out: a woman who ate well and exercised, yet still felt constantly hungry. Another: a man whose weight returned again and again, despite his best efforts.

These weren’t outliers. They were patterns.

“Many arrive thinking they’ve failed,” she says. “Part of our job is helping them see – they didn’t do anything wrong. Their biology is part of the story.”

That shift – from shame to understanding – is now embedded in every part of the clinic’s approach. And for Kirsi, it’s more than strategy. It’s a model for the future.

“Science without dignity is incomplete,” she says. “And if we want better outcomes, we need care without judgment.”

Let’s talk to Tommy

Behind every scientific insight is a team – and in Kirsi Pietiläinen’s case, a community. Her lab isn’t built on hierarchy, but on harmony, where curiosity, kindness, and collaboration drive the work forward.

“There’s no way I could do this alone,” she says. “Obesity research is too complex. It takes biologists, clinicians, psychologists, data scientists. It takes all of us.”

In her group, problems are discussed openly, and respect is non-negotiable.

“Maybe I help set the tone,” she says. “But the atmosphere comes from the people. We respect each other. We like each other. And that matters.”

Her belief in collaboration was shaped early by her mentor, Professor Aila Rissanen, who not only guided her research but helped her find her place in the international obesity science community.

“I still remember her saying, ‘Let’s talk to Tommy’ – Tommy Visscher, another young researcher like me at the time. But the person who really moved things forward, if I remember correctly, was Euan Woodward at EASO.”

Together, they helped launch something new: a European space for early-career obesity researchers.

“What began as Young Investigators United is now the Early Career Network – a vibrant, supportive community.”

And just like that, another community took root – built not just on science, but on shared purpose.

Letting go of shame, embracing biology

That experience – rooted in both scientific rigor and human connection – now shapes how Kirsi mentors others.

“There was always a firm ground under me,” she says. “Now I try to provide that for others.”

Because for Kirsi, science isn’t just about solving problems. It’s about helping people move forward – together.

But her story isn’t just about the lab. It’s also about how she changed – and how she sees obesity now.

If you ask Kirsi how her understanding has evolved, she won’t give you a slogan. She’ll offer a shift in perspective.

“Now I wear two sets of glasses,” she says. “One lens focuses on the mitochondria. The other sees the person living with obesity. I need both to really understand what’s going on.”

The goal is health, not ideals

What began as a study of invisible signals in fat tissue has grown into something much larger: a mission to reshape how science and society approach weight, health, and human biology.

And at the core of that mission is a critical distinction: body weight and health are related – but not the same.

“Yes, weight loss can improve health,” Kirsi says. “Especially for people with conditions like type 2 diabetes or cardiovascular risk. But body size doesn’t always reflect someone’s health, and we need to stop pretending it does.”

Her research focuses on what's happening inside the body: the tiny energy producers in cells, hormones that control hunger, and how our bodies manage energy. The goal isn’t to change bodies to fit ideals – it’s to understand what’s driving the system, and how to support it.

“Every choice we make – eating well, sleeping better, moving – can help our metabolic health,” she says. “Even if the number on the scale doesn’t change.”

That, for her, is the shift medicine needs: from chasing thinness to supporting health. From blaming individuals to understanding biology. From shame to science – with dignity, and with care.

Finding power in working with biology

Kirsi Pietiläinen isn’t interested in chasing ideal body sizes. Her goal is simpler – and deeper.

“I want to understand how the body works,” she says. “And how we can support it when it’s out of balance.”

That support begins with shifting the lens. Not away from health – but away from judgment. Weight can matter. But it’s not the whole story.

“We should stop treating weight like a verdict,” she says. “It’s one piece of a complex system that varies from person to person. What people need is thoughtful, stigma-free care.”

Her science speaks to that complexity. From the smallest structures in fat cells to the systems that govern public health, she’s spent decades tracing the hidden forces that shape energy, appetite, and weight.

“I’ve looked inside these layers – from the mitochondria to the clinic to the health system,” she says. “And I’ve seen that most people are trying. They don’t need blame. They need biology-informed support.”

Her work is already changing how obesity care is designed – favouring long-term support, personalised treatment, and compassionate language. And on a broader scale, it could help shift public health toward metabolic health, not just weight loss.

That belief now drives everything she builds: programs, policies, educational tools.

The finding she once kept in a drawer has become something much larger: a call for change.

Her hesitation has become clarity. Her science – rooted in biology, compassion, and precision – is helping people see what medicine once missed:

What the body is trying to do. And how to help it do better.

It’s not their fault

Health is more than body weight. It’s shaped by biology – often beyond conscious control.

“We’re not powerless in the face of obesity,” Kirsi says. “But we become powerful when we work with the body, not against it.”

That belief now shapes how she speaks to patients.

“With this symptom you have – your appetite – it often tells me there’s some kind of system error,” she explains. “Usually in the appetite centre of the brain, but sometimes it’s a lack of gut hormones.”

And even that simple recognition can lift a burden.

“It’s not their fault,” she says. “It’s definitely not their choice.”

That’s the future she’s building. A future of dignity. Of support. Of health – at every size, and every step.