Could Obesity Be An Irreversible Condition?

by Dr Sam Girgis on November 1, 2012

Obesity is becoming an increasingly prevalent problem and affects over 500 million people worldwide.  Obesity has also reached epidemic proportions among children and is estimated to affect 43 million children throughout the world.  Being overweight and obese increases the risk of type 2 diabetes, high blood pressure, heart disease, stroke, and some types of cancer.  The etiology of obesity is multifactorial and diverse, but the end result is the same – excess energy is stored in the form of fat.  Dieting and exercise can help with weight loss and the health benefits of maintaining a normal weight are enormous, and can prevent a number of chronic medical problems.

Many individuals can lose weight and gain the health benefits, but keeping the weight off is difficult.  After one year, many dieters who have lost weight will have regained a majority of it back.  In addition, many dieters often swing back and forth between weight gain and weight loss due to the difficulty with maintaining weight loss.  Recent research suggests that the longer obesity is present, the more difficult it is to maintain weight loss due to a physiologic process where the body’s set weight is reprogrammed to a higher point.

Researchers, led by Dr. Malcolm J. Low from the University of Michigan, have found that weight loss is more difficult to maintain when obesity has been present for a longer period of time during the course of a lifetime.  The results of their study were published online ahead of print in the Journal of Clinical Investigation.  The researchers generated a genetic model of early onset obesity in mice by reversibly knocking out proopiomelanocortin (Pomc) expression in the hypothalamus.  Knocking out Pomc expression causes hyperphagia and obesity, but reactivating Pomc expression results in weight loss.  The researchers found that the longer the mice remained obese, the more difficult is was for weight loss to occur after reactivation of Pomc expression.  This suggests that chronic obesity causes a resetting of the body weight to a higher point that is more difficult to change by dieting and exercise.

The authors wrote, “We rescued hypothalamic Pomc in mice with different degrees of overweight and found marked improvements in food intake, body weight, fat deposits, and fasting glucose even in cases of extreme obesity. However, increasing levels of overweight at the time of genetic rescue progressively reduced the ability of mice to achieve a normal body weight”.

The authors also wrote, “…our results show for the first time to our knowledge that obesity is a primary condition that permanently alters the normal body weight set point by imposing a maladaptive allostatic state that ultimately defends a greater body weight”.

The authors concluded, “…our findings show that obesity is a self-perpetuating condition and reinforce the importance of early consultation and weight management in children to prevent obesity, especially when taking into account that the probability of adult obesity exceeds 50% in people who were overweight at 6 years of age”.

In an accompanying editorial it was commented, “A key point of the work of Bumaschny et al. is the potential importance of early intervention for the effective treatment of obesity and its associated comorbid conditions. This is particularly relevant in our society today. For example, more than one-third of children and adolescents are overweight or obese in the United States, and the rates are increasing. If left unmanaged, obesity in childhood is likely to persist into adulthood, and, as indicated by Bumaschny et al., these individuals may become resistant to later medical interventions”.

So, is obesity an irreversible condition?  The answer is no, it is not irreversible.  As the results of this study point out though, the longer obesity is present during the course of a lifetime, the more difficult it is to reverse to a normal body weight.  Chronic or long standing obesity causes changes in how the brain regulates energy utilization and expenditure and results in a resetting of the body weight to a higher point.  This fact is important, and explains why some dieters invariably regain the weight that they have lost.  These findings have public health implications because they point out the importance of addressing obesity in early childhood.  If not addressed in early life, obesity tends to become increasingly difficult to reverse as pointed out by the results of this study.



Viviana F. Bumaschny et al. “Obesity-programmed mice are rescued by early genetic interventionJ Clin Invest. 2012; 122(11). doi:10.1172/JCI62543

Chen Liu and Joel K. Elmquist “Tipping the scales early: probing the long-term effect of obesityJ Clin Invest. 2012; 122(11):3840–3842. doi:10.1172/JCI66409

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