Over millions of years, humans got remarkably good at storing excess energy as fat. To survive perilous stretches of scarcity and famine, our brains evolved to view calorie-dense foods as highly rewarding, and our biology encourages us to eat as much as possible when we encounter them.

Fast forward to the modern world, and those kinds of foods are much more readily available, but our brains’ regulatory mechanisms never caught up.1 What was once an evolutionary advantage now works against us. The body works hard to keep the weight we gain, because losing it, runs counter to a biology hardwired when most of our days were spent hunting and gathering.2

“It’s a constant battle,” says Dr. Manige Konig, Vice President and Obesity Development Lead at Pfizer. Konig explains that our bodies activate biological mechanisms that defend body weight, a concept often described as a weight “set point.”

The body will stubbornly resist efforts to get below its set point with a range of mechanisms. If you lower your caloric intake by eating less, for instance, the body can respond by lowering your metabolic rate in order to burn less energy. And in some individuals, increased physical activity can be accompanied by compensatory increases in appetite.3

This former evolutionary advantage can now jeopardize our health. Excess body fat can increase the risk of around 200 comorbidities such as heart disease, stroke, several cancers, liver problems, and Type 2 Diabetes.4 Obesity has an impact on almost every system that keeps us alive.5

It’s also common. In 2022, about 890 million adults worldwide—that’s one out of every eight—were living with obesity, according to the World Health Organization.6

Adult obesity has more than doubled since 1990. Among adolescents, it’s quadrupled.6 The World Obesity Federation projects more than 1 billion people will be living with obesity by 2030.7

In the U.S. alone, the CDC data collected between 2021 and 2023 found that about 40 percent of adults were living with obesity, with no meaningful difference between men and women.8

And yet obesity is still widely treated as a personal failing. The science says something else entirely.

A Disease, Not a Decision

In recent years, the medical research community has come to understand obesity as a chronic, complex, multifactorial disease that requires long-term management.

“There's still a lack of understanding that obesity is really a disease and a condition,” Konig says. “It’s not the patient's fault. It's the genetic profile, the environmental profile, the gut profile. It’s so multifactorial.”

Despite substantial evidence that weight gain can be a result of myriad interconnected factors, a number of which are outside of our control, negative attitudes toward people living with obesity are still pervasive in the U.S. That weight stigma carries very real consequences for those forced to endure it in workplaces, educational institutions, medical offices, or even at home in close interpersonal relationships.9

Once even considered an incentive for weight loss, scientists now know that stigma can have adverse physical and mental health outcomes for patients, creating a negative feedback loop that makes weight loss even harder. The stigma can dampen psychosocial wellbeing, lead to a depressed mood, increase risk factors, and lower self-esteem.9,10

Weight stigma also increases stress, which can play a major role in developing obesity, according to Konig. That’s because it drives higher-calorie comfort eating and triggers spikes in cortisol—a stress hormone that can contribute significantly to setting the body’s metabolic rate and determining where fat gets stored.11

Studies suggest that individuals who experience weight discrimination are more likely to gain weight over time and progress from overweight to obesity. And because weight stigma can show up in clinical settings, too, many people delay or choose not to seek treatment at all.10

When Konig was a practicing physician, many of her patients felt too ashamed to raise the issue with their doctors. “They didn’t really want to talk about it,” Konig says. Many had internalized the belief that obesity was the consequence of their personal choices viewing their condition as a personal moral failure or a lack of self-discipline, so they’d blame themselves.

What Actually Drives Weight Gain

If willpower isn’t the driver of obesity, then what is? The answer is as complicated as the human body itself, but Konig points to several primary, interconnected factors:

Genes: Scientists have linked between 200 and 500 different genes to obesity, finding they can affect everything from fat storage, to nutrient metabolism, to the signals that help regulate hunger and satiety.12 “So many genes are affected,” says Konig, “and this is why it is so difficult to find a cure for the disease.”

Stress: In addition to raising cortisol levels, stress increases appetite and cravings for calorie-dense food while interfering with the cognitive processes involved in self-regulation.13

Sleep: Insufficient or disrupted sleep—a particular problem for night-shift workers—tips the balance of appetite-regulating hormones, raising ghrelin while lowering leptin, which increases the drive to eat. Sleep deprivation also compounds stress and weakens cognitive control, making emotional eating more likely.13

The Gut: The human gut microbiome is an astonishingly vast ecosystem. Scientists estimate it contains around 100 trillion microbial cells, more than the number of stars in our galaxy.14,15,16 When those bacteria break down the food we eat, they produce compounds that influence appetite, inflammation, insulin sensitivity, and how the body stores fat.15

Circumstance: “Socioeconomics is a big, big factor,” says Konig, “Healthy eating, of course, can really help with your weight management. But a lot of patients don’t have access to healthy food because it’s expensive.”

And once weight is gained, biology guards it. Research suggests adipose tissue retains a kind of “epigenetic memory” of obesity that persists after weight loss and makes people more susceptible to regaining it—one possible mechanism behind the “yo-yo effect” so many people describe.17

All of which helps explain why the standard weight-loss advice so often fails.

A Standard of Care Emerges

There’s reason for optimism. In 2025, the Obesity Association, a division of the American Diabetes Association, began publishing Standards of Care in Overweight and Obesity, providing comprehensive, evidence-based recommendations for the prevention, diagnosis, and management of obesity.18,19 While several professional societies have previously published obesity management guidelines, these Standards of Care represent an important step toward broader recognition of obesity as a chronic disease requiring evidence-based, long-term management.

“This is already a very big plus,” Konig says. “We’re moving in the right direction, but much more remains to be done.”

The stigma recommendations are practical. The Standards of Care state that all healthcare professionals and staff should be trained to recognize weight bias, with training beginning early and continuing through practice. Clinicians should also ask permission before discussing weight, use person-centered and non-judgmental language, and engage patients in shared decision-making.19

Much of it boils down to empathy. “It’s a real struggle for these patients,” Konig says. “Having this empathy or compassion without negative judgement—this is sometimes what they need.”

She also points to the value of a team: a nutritionist, a trainer who can build an appropriate exercise plan, and a physician managing the medical side. “Multidisciplinary is actually the key moving forward to see long-term success,” she says.

The Future of Obesity Care

Because obesity is multifactorial, no two patients experience it in quite the same way, and the same is true for treatment. That’s why personalized therapeutics are so important, because the same treatment approach that works for one patient might not suit another.

“Because we have a much greater understanding of obesity, it’s now becoming much more important to tailor the treatment based on every patient's need,” Konig says.

Before we can truly do that well, she says, we still have work to do.

“We still need to learn more about the complexity of obesity as a disease,” Konig says. “Tailoring therapy based on underlying pathophysiology and personalized treatment is the way to go.”

But the picture is coming into focus. A great deal of what drives obesity, she notes, originates in the brain, and researchers are steadily identifying more of the mechanisms involved.

“I think from the science perspective,” Konig says, “we are really getting there.”