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In my post last Monday exploring causes of obesity, I discussed that we are slowly gaining a better appreciation of the role of genetics in the development of obesity and mentioned the FTO gene, but lamented that “we are far from a thorough understanding of the role of genetics in the obesity epidemic.” Well, as of Wednesday, we are one step closer. To great media fanfare, the New England Journal of Medicine, the nation’s premier medical journal, released an article describing new discoveries related to the FTO gene and its link to obesity, bringing with it hopes for new treatment options.

Population-based genetic studies had already shown that certain versions of the FTO gene were linked to obesity, but it was unclear how, until now. To understand the FTO gene, you first must know that not all fat cells are created equal.  Instead there are two main types. White fat does what fat is best known for, acting as a storage depot for your extra calories and preventing you from fitting into that pair of jeans you wore last year. You don’t burn much energy to maintain your white fat — it basically sits there until you use it (or don’t), keeping us well-padded for the next famine. In contrast, beige or brown fat, as it is called, is metabolically active. These fat cells actually burn energy to create heat. Over the course of your life, your body is making more fat cells. Creating more white fat was thought to predispose individuals to a greater risk of obesity, while more beige fat would likely have the opposite effect.

In the article released this week, scientists showed through a series of deft experiments that the FTO gene is involved in determining whether a nondescript fat cell precursor becomes a white cell or a beige cell. Furthermore,  they demonstrated that the version of the FTO gene linked to obesity resulted in the creation of far more white fat cells than beige fat cells. And they were able to show that by genetically manipulating the FTO pathway in mice, they could produce mice that could remain svelte even when fed a high-fat diet.

This is exciting for a number of reasons. While obesity affects 1 in 3 Americans, costing us some $150 billion (yes, with a b) annually in medical expenses and contributing to such health problems as heart disease, diabetes, and stroke, medications to target obesity itself have been consistently disappointing. This article opens the door to new possible pharmacological targets to address this growing epidemic.

However, as with many such well-publicized scientific discoveries, the degree of fanfare is bound to lead to disappointment. First, there is the issue of just how big a role this is really playing. For example, while 44 percent of Europeans have the obesity-prone version of the FTO gene, only 5 percent of people with African ancestry do. But rates of obesity approach 50 percent in African-Americans, compared with about 33 percent in Caucasians. Looking at it another way, some studies have shown that the difference between having the fat-prone version of the gene or not is about 7 pounds. While seven pounds can make a significant difference in an individual’s health, it is unlikely to account for the majority of the extra pounds an individual may be carrying. Finally, while some news articles offer the possibility that someday we could just “flip a switch” to change from making white fat to making beige fat, this is years — likely decades — down the road, if it ever becomes a possibility.  Drugs targeting specific genetic pathways are in their infancy.  Despite these reservations, this article represents a significant advancement in understanding a piece of the obesity puzzle and fosters hope for future innovations.

References

Claussnitzer M, Dankel SN, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J, Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M. FTO Obesity Variant Circuitry and Adipocyte Browning in Humans. N Engl J Med. 2015 Aug 19.

Rosen CJ, Ingelfinger JR.  Unraveling the Function of FTO Variants.  N Engl J Med. 2015 Aug 19.