Why Is Losing Weight So Difficult?

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Obesity has reached critical levels globally. The World Health Organization reports that 2.5 billion adults were overweight as of 2022 and 890 million were living with obesity. This indicates almost half the adults in the world (43%) are overweight and 16% may be obese. It is estimated that by 2025, more than 1.5 billion adults will be living with obesity.

Children are not faring any better. Over 390 million children and adolescents (aged 5-19) were overweight in 2022, including 160 million who were obese. Among them, 37 million children under the age of 5 were overweight. These figures suggest that 1 in 5 children are now overweight or obese, which is a significant increase compared to past decades. And the rate of obesity is increasing rapidly throughout the world. Adult obesity has more than doubled since 1990 and adolescent obesity has quadrupled.

Obesity is associated with an increased risk of type-2 diabetes and heart disease. Obesity can also affect bone health and reproduction and increase the risk of some types of cancers. In addition to these health issues, obese individuals tend to suffer from a reduced quality of life due to impairments in sleeping and mobility.

How Successful Are Weight Loss Strategies?

The success rates of weight loss strategies vary significantly depending on the method, but many people find it difficult to achieve and maintain significant weight loss. Lifestyle interventions such as dietary changes and exercise are commonly employed. However, even when these methods help with weight loss, maintaining it can be difficult. A review of 29 studies found that after five years, more than 80% of lost weight had been regained.

A popular recent approach involves the use of GLP-1 receptor agonists. These medications mimic the action of glucagon-like peptide-1, a hormone that regulates appetite, blood sugar, and insulin secretion. Drugs in this class, such as semaglutide (Wegovy/Ozempic) and tirzepatide (Mounjaro), are generally used to treat Type 2 diabetes, but recently have gained widespread appeal as weight-loss drugs. They work by slowing gastric emptying, reducing hunger, and enhancing feelings of fullness, which helps reduce calorie intake.

Clinical trials have shown that GLP-1 agonists can lead to significant weight loss. Semaglutide results in an average weight loss of 15% of total body weight, and tirzepatide can deliver weight loss of up to 22.5% over a 68-week period—when combined with effective lifestyle interventions. However, continued use of GLP-1 agonists is critical for maintaining this weight loss. When these medications are stopped, individuals often regain much of their lost weight within 12 months. In addition, these medicines can have significant side effects that include nausea, vomiting, and diarrhea.

Why is it so difficult to maintain weight loss?

Long-term studies indicate that maintaining weight loss is difficult. A study published in the American Journal of Clinical Nutrition found that only about 20% of people in the general population are successful at long-term weight loss maintenance, indicating that the majority regain their lost weight over time. But why is it so hard to keep the weight off once you lose it? One reason may be that fat cells possess memory, and these cells "remember" what it is like to be obese. This may help explain the “yo-yo effect” that occurs when you lose weight, then gain it back again over time.

A team of Swiss researchers have discovered that obesity produces changes in fat cells that persist even after you lose weight. These changes cause fat cells to remember their prior state of obesity. This discovery came after the team studied two groups of people: one group that had never been obese and a second group that had been severely obese. Fat cells taken from both groups revealed that some of these cells continued to form scar-like tissue (i.e. fibrosis) and produced inflammation even after the obese patients underwent weight-reduction surgery.

In another experiment, the same researchers studied obese mice. They began by putting obese mice on a weight-loss diet. Once the obese mice lost weight, they were fed a high-fat diet for one month. The same high-fat diet was also fed to mice that had never been obese. Can you imagine what happened? The previously obese mice gained an average of 14 grams whereas the mice that had never been obese gained an average of only 5 grams. Similarly, when fat cells from the previously obese mice were grown in a lab, these cells absorbed more sugar and fat than cells from the mice that were never obese. These findings indicate that fat cells can remember their previous obese state. This type of memory is referred to as epigenetic obesogenic memory (i.e. memory that causes obesity as the result of epigenetic changes).

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Future Implications

Weight-loss studies investigating memory in fat cells suggest that it may be more effective to prevent obesity than to try to reverse it. This highlights the importance of healthy nutrition, especially for children, who are increasingly at risk of being overweight.

The good news is that awareness of the importance of a healthy diet and an active lifestyle is increasing but it remains important to educate ourselves about nutrition rather than rely only on our physician for dietary advice, as many doctors may have received only minimal training in medical school about nutrition.

Perhaps future research may discover ways to alter obesogenic memory. This would allow fat cells to forget about their previous obese state and instead remember how to maintain a healthy weight. In the meantime, however, it is likely that obesity will continue to be a major health issue.