For centuries, being overweight has been believed to be the result of a weakness of character — the inability of obese people to control their impulses — and weight control, a simple matter of arithmetic: what you consume minus what you burn. “Eat less, exercise more,” goes the popular saying. However, scientific efforts in recent decades have proven that such a remedy may be compelling, but it is not a solution. One of the most relevant discoveries regarding the regulation of appetite, which causes some to be hungry at all hours and others to be effortlessly ascetic, was leptin, the so-called satiety hormone. In an interview in EL PAÍS, Jeffrey Friedman, the man who discovered the molecule in 1994, claimed that obese people are obese because they eat too much, but he referred back to the central question: “Why do they eat too much?”
Leptin is part of the molecular mechanism that instructs us when to eat and when to stop, and not all of us receive the same signals. “Our weight is regulated by genes, much like our height. You wouldn’t ask someone who is 6′2″ to be 6′3″, because that’s just the way they are,” explains Friedman. In recent decades, the percentage of obese and overweight people has increased. Although some may suggest that this pandemic is a reflection of a decadent society teeming with willpowerless individuals, scientists who study the phenomenon extensively know that this is untrue and that the solutions lie beyond proverbs and common sense.
In its most recent August issue, Science Magazine published an analysis by several experts with some surprising insights. Despite significant advances in our understanding of the disease, including the discovery of leptin, “there is limited consensus on the causes” of the obesity pandemic, the authors write, stating that, “although it is often claimed that increasing sedentary lifestyles are a major cause of the obesity pandemic, this is by no means clear and the current evidence does not back up this conclusion.” John Speakman, one of the paper’s authors, argues via email that “the data show that as people become more obese, they become less active, but the cost of moving increases.” “Ultimately, these two factors balance out, and when you take the effect of body mass out of the equation, as the pandemic has progressed, the energy consumed through physical activity has increased slightly [since the 1980s],” he says.
We are not like bank accounts
In another article published this year, the researcher from the University of Aberdeen (U.K.) attributed part of the imbalance between energy consumption and expenditure that results in obesity to a decline in the basal metabolic rate, the amount of energy expended at rest, over the last 30 years. One strategy to combat the pandemic would be to increase this, but what has caused the decline is unclear. The authors speculate that less exposure to infectious diseases may have reduced our immune defense capacity or that dietary changes, such as a reduction in saturated fat consumption, may have had something to do with it.
The recognition of the complexity of the problem has an initial consequence, namely a change in the treatment of patients. “In the traditional approach to obesity, when it was treated as if it were a checking account, with inflows and outflows, something was done that is not usually done with other diseases: the blame was placed on the patient,” points out Cristóbal Morales, endocrinologist at the Virgen de la Macarena hospital in Seville. “Now, we view it as a social disease where there is an influence between genes and an obesogenic environment with much variability between people,” he adds. Decades of treating the disease as one of personal responsibility have shown that this is not the way to battle the pandemic.
A second consequence, which is perhaps more long-term, is the use of personalized medicine in the treatment of obesity. “Currently, there is no distinction, and people with obesity are all classified in the same group and then, as with all diseases, not all patients respond in the same way to different treatments,” explains Rubén Nogueiras, researcher at the University of Santiago de Compostela. “With the new anti-obesity drugs, some patients lose as much as 20% weight, as with bariatric surgery, others do not respond as well, and others do not respond at all,” Nogueiras continues. “The ultimate goal is to classify patients better in order to provide personalized treatment,” he concludes.
Organizations such as the Mayo Clinic, in Rochester, Minnesota, are already proposing the segmentation of people with obesity into four main types. First, there is the “hungry brain,” influenced by signals between the brain and the gut, which requires an abnormal number of calories to reach fullness. Second, there is “emotional hunger,” when food is used to cope with negative and positive emotions. Third, comes the “hungry stomach,” when fullness does not last as long as it should. And fourth, “slow burn,” for people with a decreased metabolic rate.
Metabolism, genes and environment
Manuel Tena-Sempere, a researcher at the University of Córdoba, also points out that the components that control body weight, such as leptin, are not only related to factors that contribute to maintaining a balanced weight. “It was believed that some hormones such as leptin increased almost automatically upon ingestion, but it has been found that their levels are related to aspects such as the pleasure that comes from eating, and this explains why not all individuals follow the same eating patterns. These components make some people inclined to eat in a more compulsive way,” he explains.
The authors of the Science Magazine article issue a warning about another type of arithmetical simplification that can arise when it comes to knowledge on obesity. The different forms of energy expenditure [physical activity, resting metabolic rate, and thermal regulation, with the critical role of brown fat] may not be related to each other. Therefore, they can be added and subtracted as though the changes occurring in each of them were independent of the rest. “Raising one aspect of output may cause compensatory decreases in other components or changes in intake,” they explain.
“Obesity as a disease should not be confused with the social desire to be thin.”Guadalupe Sabio, National Center for Cardiovascular Research of the Carlos III Institute
In this disease, which is the result of the interplay between genes and environment, some issues are not well understood, such as the ability of ultra-processed food to drive us to consume more energy. Some combinations of nutrients that do not exist in nature and reprogram brain segments that regulate motivation and reward lead to overconsumption, but the mechanisms involved are unclear. The influence of sweeteners on weight gain and obesity-associated diseases is also unknown. “They affect glucose metabolism. It significantly impairs insulin sensitivity and promotes insulin resistance and the onset of type two diabetes,” says Nogueiras.
Industrial chemical compounds
Other elements believed to play a role in the obesity pandemic are endocrine disruptors — a large number of chemical compounds such as bisphenol A or PFAS ― which are used in plastic packaging, canned food lids and many other products. These substances “alter hormonal function, and a large part of body weight is regulated by hormones,” explains Nogueiras. “Some endocrine disruptors also have an impact on obesity-associated conditions such as fatty liver disease or diabetes. This is a domain where we still need to learn more, but the results that are appearing are pointing in the same direction,” he adds. Guadalupe Sabio, a researcher at the National Center for Cardiovascular Research of the Carlos III Institute in Madrid, agrees: “Hormonal disorders are very important. This can be seen in women during menopause, which changes where the fat accumulates or whether the fat is going to be inflamed.”
A greater understanding of the role of some industrial products in the pandemic would provide a case for regulating their use, as is the situation with ultra-processed foods. In addition to leveraging the efficacy of bariatric surgery or new obesity medications — the successful GLP-1 agonists — public policies will be required to control the problem. For starters, Sabio stresses the importance of “treating obesity as a disease and not blaming the patient,” although she points out that “obesity as a disease should not be confused with the social desire to be thin.” For the time being, governments do not believe obesity is a disease, and they’re not funding GLP-1 agonists to treat it.
The article by Speakman and colleagues discusses the social dimension of the disease and outlines some of the mysteries surrounding it. In wealthier countries, the poor are more likely to be obese than the rich, but in the poor nations it is the other way around. The stress and stigma associated with being overweight may favor the progression of obesity. In this regard, obesity carries an important hereditary factor, owing to genetics, but also to social conditions. Tena indicates factors such as gender: “Historically, metabolism studies have been conducted in males and we have seen that hormonal factors are central to the predisposition to obesity.” And he believes it is vital to anticipate “early risks that are inherited from the individual’s mother, father or grandfather and that could be reduced by adopting preventive measures.” Speakman says that studies in mice “show that maternal obesity and diet affect the susceptibility of offspring to obesity, perhaps through epigenetic mechanisms, but it is uncertain whether this applies to humans.”
Despite the numerous uncertainties surrounding the greatest pandemic of the industrial age, experts agree on the considerable progress made in recent times. These advances pave the way for effective drugs and help to move beyond simplistic and unhelpful approaches. Individual responsibility will still be important, as it is in the management of any chronic ailment, but it must not be the focal point. According to data from the Spanish Society for the Study of Obesity, about 80% of attempted diets end in failure and the figures may be even worse if the follow-up process is carried out in the very long term. Rather than thinking that the blame lies with the people who do not apply the solutions offered to them, perhaps it is time to ask ourselves if we really understand the problem.
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