A complex puzzle of biology, environment, and society
For decades, the message has been simple: eat less, move more. Yet, as global obesity rates continue to climb, this conventional wisdom has proven woefully inadequate. Once considered a simple failure of willpower, obesity has now been recognized by the World Health Organization as a chronic complex disease—one that has more than doubled in adults and quadrupled in adolescents since 1990 1 . This article explores the fascinating scientific detective story behind one of our most pervasive, yet least understood, public health crises.
The statistics surrounding obesity are staggering. In 2022, approximately 2.5 billion adults worldwide were overweight, with 890 million of them living with obesity 1 . This means 43% of the global adult population carries excess weight, with profound implications for health, economies, and healthcare systems.
The economic impact is equally dramatic. If no effective interventions are implemented, the global costs of overweight and obesity are predicted to reach US$3 trillion per year by 2030 and more than US$18 trillion by 2060 1 .
Adults worldwide were overweight in 2022
| Population Group | 1990 Prevalence | 2022 Prevalence | Increase |
|---|---|---|---|
| Adults (obesity) | ~8% (est. based on doubling) | 16% | More than doubled |
| Adolescents (obesity) | 2% (31 million) | 8% (160 million) | Quadrupled |
| Children 5-19 (overweight including obesity) | 8% | 20% | 2.5-fold increase |
| Children under 5 (overweight) | Not specified | 35 million (2024) | Steady increase |
Table 1: Dramatic increases in global obesity prevalence across age groups based on WHO data 1
What makes these numbers particularly puzzling is that this explosion has occurred within a relatively brief timeframe. Our genes haven't changed, but something in our environment has shifted dramatically—and scientists are racing to understand what.
For years, the prevailing theory was that people with obesity simply enjoyed high-calorie foods too much, leading to overeating. However, groundbreaking research from UC Berkeley has turned this assumption on its head 2 .
Researchers noticed something paradoxical in their lab: mice raised on a high-fat diet strongly preferred high-fat chow in their home cages, yet when given access to special high-calorie treats, they showed much less interest than mice on a normal diet 2 . The obese mice seemed to be eating not out of pleasure, but perhaps out of habit or boredom.
Brain scans of individuals with obesity show reduced activity in pleasure-related brain regions when presented with food 2 .
A brain peptide called neurotensin was significantly reduced in the obese mice. Neurotensin interacts with the dopamine system, which plays a crucial role in reward and motivation 2 .
"We found that this same feeling occurs in mice on a normal diet, but is missing in those on a high-fat diet. They may keep eating out of habit or boredom, rather than genuine enjoyment."
The researchers tested two approaches to restore neurotensin levels. When obese mice were switched to a normal diet for two weeks, their neurotensin levels returned to normal, and they regained interest in high-calorie foods. When neurotensin was artificially restored using genetic techniques, the mice not only lost weight but also showed reduced anxiety and improved mobility 2 .
This research provides a potential explanation for why people with obesity might struggle to change eating patterns—the brain's reward system itself may be altered by chronic consumption of high-fat foods.
Modern obesity research relies on sophisticated tools that allow scientists to unravel the complexity of fat tissue, brain circuits, and genetic regulators.
| Tool/Technology | Function in Obesity Research |
|---|---|
| CRISPR-Cas9 Gene Editing | Identifies genes and microproteins regulating fat cell development and lipid storage 5 |
| Single-cell RNA sequencing | Maps different cell types within fat tissue, identifying previously unknown subtypes |
| Optogenetics | Controls specific brain circuits with light to understand neural pathways governing eating behavior 2 |
| Body Mass Index (BMI) | Standardized screening tool for weight status (≥25 = overweight; ≥30 = obesity) 1 |
| Adipose Tissue Biopsies | Allows study of different fat depots (subcutaneous vs. visceral) and their cellular composition |
Table 2: Key technologies enabling advanced obesity research
These tools have revealed that obesity is far more complex than a simple equation of calories in versus calories out. Fat tissue, once considered a passive storage depot, is now known to be an active endocrine organ that produces hundreds of signaling molecules .
The most compelling evidence that obesity cannot be reduced to individual choice comes from its rapid global spread. The shift in our environment has been described as creating "obesogenic environments" where unhealthy choices become the default 1 .
Multiple factors have converged to create the obesity epidemic 1 4 :
Structural factors have made healthy, sustainable food less available and affordable while energy-dense, micronutrient-poor foods have become widely accessible
Lack of safe spaces for physical activity and increased sedentary behaviors
Poverty reduction and urbanization have changed eating patterns and activity levels
Potential role of obesogenic chemicals with endocrine-disrupting properties in our food chain
Many countries now face a "double burden of malnutrition"—where undernutrition and obesity coexist within the same communities, sometimes even the same households 1 .
Why do some people living in obesogenic environments develop obesity while others don't?
What explains the variation in where individuals store fat, with visceral (abdominal) fat being more metabolically harmful?
Why is weight loss maintenance so difficult, with biological adaptations promoting weight regain?
Recent discoveries may point toward answers. Scientists at the Salk Institute have used CRISPR screening to identify dozens of previously unknown microproteins that regulate fat cell growth and lipid storage 5 . One confirmed microprotein, Gm8773, appears to promote fat storage by increasing the size of lipid droplets in fat cells 5 .
Similarly, an international research team has identified unique subpopulations of fat cells with more complex functions than previously known . The relative proportion of these unique cells appears to correlate with the severity of insulin resistance, potentially paving the way for more personalized obesity treatments.
| Research Approach | Potential Application |
|---|---|
| Neurotensin pathway manipulation | Restoring healthy eating motivation in obesity 2 |
| Microprotein-based therapeutics | New drugs targeting newly discovered regulators of fat storage 5 |
| Fat cell subpopulation mapping | Personalized risk assessment for obesity complications |
| Natural experiment methodologies | Better evaluation of population-level interventions 3 6 |
Table 3: Promising avenues for future obesity research and treatment
The science clearly shows that obesity is not a moral failing but a complex disease involving interactions between genetics, neurobiology, metabolism, and our environment. The most effective solutions will likely come from addressing the environmental drivers while developing targeted biological interventions.
Public health policies that show promise include 9 :
Regulations to provide clear nutritional information
Restrictions on marketing of unhealthy foods to children
Planning that promotes physical activity through walkable communities
Taxes on sugar-sweetened beverages to discourage consumption
Blame and stigma have no place in the solution. We need compassionate, science-based approaches.
"The diversity of fat cells in the different fat tissues in humans is more complex, interesting, and surprising than we previously thought."
As we continue to unravel the mystery of the obesity epidemic, one thing becomes increasingly clear: blame and stigma have no place in the solution. Instead, we need compassionate, science-based approaches that address the biological, environmental, and social dimensions of this pressing global health challenge.
The path forward will require recognizing what Prof. Rudich notes: "The diversity of fat cells in the different fat tissues in humans is more complex, interesting, and surprising than we previously thought" . By embracing this complexity, we can move closer to solving the puzzle of obesity.