Why are we gaining weight?

Ali Araghi, MD.

Background: The Obesity Puzzle

Obesity rates are rising globally, and experts still debate the leading causes. Traditional explanations like overeating and moving too little don’t fully account for the problem. For example, national data show that energy consumption hasn’t increased in recent decades, yet obesity rates continue to climb. There is also no consensus among scientists, which has led to confusion and skepticism about obesity prevention and treatment.

When Does Obesity Begin?

Obesity is a complex neuroendocrine disease involving hormones and the brain’s regulation of body weight. The groundwork for obesity can be laid before birth (in utero) or during early childhood. Factors like a mother’s weight before pregnancy, parental nutrition, and exposure to certain chemicals can affect a child’s risk of obesity later in life. These influences can even be passed down through generations via changes in gene expression (epigenetics).

Four Main Models of Obesity

Four major scientific models try to explain obesity:

1. Energy Balance Model (EBM):
   • Obesity results from consuming more calories than are burned.
   • The brain regulates body weight by balancing food intake and energy expenditure.
   • Ultra-processed foods (UPF) can cause overeating and weight gain.
   • However, this model doesn’t explain why animals in captivity, or the wild, are also gaining weight, or why obesity rates rise even when calorie intake falls.
2. Carbohydrate-Insulin Model (CIM):
   • Focuses on the quality, not just the quantity, of calories.
   • Eating refined carbohydrates and sugars leads to high insulin levels, promoting fat storage.
   • This model highlights the role of insulin and how specific diets (like those high in processed carbs) can drive obesity, but the exact mechanisms remain unclear.
3. Reduction-Oxidation (REDOX) Model:
   • Emphasizes the role of reactive oxygen species (ROS) molecules produced during metabolism that signal when the body has excess fuel.
   • Normally, ROS helps regulate fat storage, insulin secretion, and appetite.
   • Too much ROS, caused by overeating or exposure to certain chemicals, can overwhelm the body’s defenses, leading to oxidative stress, inflammation, and metabolic problems that promote obesity.
   • People with obesity often have lower antioxidant capacity, making them more vulnerable to oxidative stress.
4. Obesogen Model (OBS):
   • Proposes that exposure to certain environmental chemicals (obesogens) disrupts hormonal and metabolic signaling, increasing fat storage and risk of obesity.
   • Obesogens are found in food packaging, pesticides, plastics, personal care products, air pollution, and pharmaceuticals.
   • Exposure can occur before birth, during childhood, or throughout life, and can have long-lasting or even transgenerational effects.
   • Obesogens can alter the number and function of fat cells, change the gut microbiome, and affect appetite and energy use.

The Integrated OBS/REDOX Model

A recent theory proposes a unified theory combining the obesogen and REDOX models. Here’s how it works:

• Obesogens (from air, food, packaging, and household products) disrupt normal hormonal signaling and increase ROS production in the body.
• The resulting false signals confuse the body’s energy regulation systems, leading to increased insulin secretion, fat storage, disrupted metabolism, and changes in appetite and energy use.
• This model incorporates elements from the EBM and CIM, recognizing that both calorie quantity and quality and environmental exposures play roles in obesity.
• The model suggests that everyone’s exposure to obesogens is widespread, and the effects depend on genetics, age, sex, lifestyle, and other factors1.

Evidence for the OBS/REDOX Model

• Hundreds of studies in animals and humans show links between obesogen exposure and increased obesity risk.
• Obesogens are now found in the air, water, food, and everyday products, making exposure nearly universal.
• The timing of increased obesogen use in society matches the timeline of rising obesity rates.
• Obesogens can explain why even animals in controlled environments are gaining weight, and why obesity can start before birth or in early childhood1.

Implications and Future Directions

• Reducing exposure to obesogens—changing food packaging, limiting certain product chemicals, and improving regulations—could be a powerful new strategy for preventing obesity.
• More research is needed to show that lowering obesogen exposure improves human metabolic health directly.

Key Takeaways

• Obesity is not just about overeating or exercising too little. It is a complex disease involving genetics, hormones, metabolism, and environmental exposures.
• Chemicals called obesogens, found in many modern products and foods, may play a significant role in driving the global obesity epidemic by disrupting the body’s normal energy regulation.
• The new integrated OBS/REDOX model explains how obesogens and oxidative stress can trigger obesity, incorporating and expanding on previous theories.
• Addressing obesogen exposure could be crucial to future obesity prevention efforts.

In Summary:
Obesity is a complicated problem that can’t be solved by focusing only on calories or carbs. The chemicals in our environment, mainly processed foods, packaging, and everyday products, may be tricking our bodies into storing more fat and disrupting our metabolism. This new theory suggests tackling these chemical exposures could help slow or reverse the obesity epidemic.

Citation:

Heindel JJ, Lustig RH, Howard S, Corkey BE. Obesogens: a unifying theory for the global rise in obesity. Int J Obes (Lond). 2024;48(3):449-460. doi:10.1038/s41366-024-01460-3