Explaining the “Obesity Paradox”

Obese people are more likely than others to develop diabetes, heart disease, and stroke, but – and here’s the paradox – they are also more likely to survive a major attack caused by one of these conditions. So what’s the explanation for this “obesity paradox”? A publication in the journal Endocrinology describes a possible answer to this question.

University of Illinois scientists showed that mice fed a high-fat diet for 12 weeks recovered from a serious event – acute deprivation of oxygen – five times faster than non-obese mice. This serious event was considered to be a model for a heart attack or stroke, leptin (the hormone secreted by fat cells) triggered the immune system to increase production of an anti-inflammatory molecule, interleukin-1 receptor antagonist (IL1-RA). The scientists believe that the immune cells (macrophages, in this case) of obese mice make more IL1-RA due to the action of leptin from the increased numbers of fat cells.

Additional studies were done to show that:

1. obese mice produce more IL1-RA
2. this IL1-RA comes from macrophages
3. normal mice given IL1-RA have accelerated recovery from hypoxia
4. blocking IL1-RA leads to blocking of this acceleration

This elegant series of studies (albeit in lab animals) supports the concept that obese people have overproduction of leptin, which stimulates production of IL1-RA, which, as an anti-inflammatory agent, can help protect against the dire results of diabetes, heart attack, or stroke.

What are the practical consequences of this hypothesis? They aren’t clear at present. But I summarize this publication as an example of how scientists proceed in trying to ‘prove’ a theory they have developed to explain a phenomenon.