Do I Look Fat in These Genes?

by Carol A. Westbrook

Are you pleasantly plump? Rubinesque? Chubby? Weight-challenged? Or, to state it bluntly, just plain fat? Have you spent a lifetime being nagged to stop eating, start exercising and lose some weight? Have you been accused of lack of willpower, laziness, watching too much TV, overeating and compulsive behavior? If you are among the 55% of Americans who are overweight, take heart. You now have an excuse: blame it on your genes.

It seems obvious that obesity runs in families; fat people have fat children, who produce fat grandchildren. Scientific studies as early as the 1980's suggested that there was more to it than merely being overfed by fat, over-eating parents; the work suggested that fat families may be that way because they have genes in common. Dr. Albert J Stunkard, a pioneering researcher at the University of Pennsylvania who died this year, did much of this early work. Stunkard showed that the weight of adopted children was closer to that of their biologic parents than of their adoptive parents. Another of his studies investigated twins, and found that identical twins–those that had the same genes–had very similar levels of obesity, whereas the similarity between non-identical twins was no greater than that between their non-twin siblings. It was pretty clear to scientists by this time that there was likely to be one or more genes that determined your level of obesity.

In spite of the compelling evidence, it has been difficult to identify the actual genes that cause us to be overweight. This is due partly to the fact that lifestyle and environment are such strong influences on our weight that they can obscure the genetic effects, making it difficult to dissociate genetic from environmental effects. But the main reason it has been difficult to find the fat gene is because there is probably not just one gene for obesity, as is the case for other diseases such as ALS (Lou Gehrig's disease). There seem to be many forms of obesity, determined by an as yet unknown number of genes, so finding an individual gene is like looking for a needle in a haystack.

Earlier this year, a group of researchers succeeded in identifying one of these genes by focusing on a single form of obesity and studying only a small number of families. Their studies, published in the New England Journal of Medicine, reported a gene mutation which was shared by all of the obese members of the families. The mutated gene, DYRK1B, seems to be involved in initiating the growth of fat cells, and in moderating the effects of insulin. The people in these families who carried the gene mutation all had abdominal obesity beginning in childhood, severe hypertension, type 2 diabetes, and high blood triglyceride levels. They had a type of obesity known as “metabolic syndrome.”

Metabolic syndrome is recognized by doctors as a combination of symptoms, including large waist size, high triglycerides (lipids), low LDL “good” cholesterol, high blood pressure, and high blood sugar. In order to meet the diagnosis of metabolic syndrome, you need to have any 3 of these 5 criteria. A person who has metabolic syndrome is five times as likely to develop diabetes, and twice as likely to develop heart disease, as someone who doesn't have it.

Metabolic syndrome is not a rare condition; in fact, it has been estimated that as many as 47 million Americans have it, though usually not as severely as the one carried by the families in the study, above. Many more Americans may actually carry a mutation in the DYRK1B gene, or in a related gene, but have not developed the symptoms… yet.

What is perplexing is why obesity continues to be on the increase in the US, despite the fact that our genetics couldn't have changed that much over the last decade or two. Clearly there is more to being fat than carrying a fat gene. As we are all aware, you have to eat to become overweight. The fault is not in our stars, it is in our diets. And our diets have changed quite a bit over the last few decades.

What's wrong with our diets? That, of course, is one of the most important health questions of today. Our diets have changed a lot over the last few decades, starting with the movement in the mid 1970's to cut down the fat that we eat, mistakenly thinking that fat was the cause of high cholesterol and lipid problems. This led to the widespread substitution of calories from fat with calories from carbohydrates, particularly high fructose corn syrup and related additives. Nowhere have the substitutions been more dramatic than in fast foods and prepared foods. A high carbohydrate diet is a disaster for someone who is at risk of metabolic syndrome; it is the quickest way to get fat.

As the number of fat people increases, we are starting to see increases in diabetes, hypertension, and knee replacements. Obesity is linked to 1 in 5 deaths in our country. Finding more of the genes that cause people to be overweight will help to identify those at risk, so they can take steps to prevent it. And better yet, these gene mutations may provide targets for the creation of drugs to reverse the condition. The pharmaceutical industry is very interested in finding these genes: imagine if you could produce a pill that 50% of the entire population would have to take every day, for the rest of their lives, to prevent them from being fat!

Sadly, we do not have this pill to reverse metabolic syndrome, at least not at the present time. So, like many other diseases that are sensitive to the foods we eat — hypertension, diabetes, gluten-sensitivity, and so on–the answer is still in controlling the diet.

But take heart. Now you can relax, forget the accusations and stop
blaming yourself. Enjoy those Christmas cookies and holiday treats today. Your diet starts on January 1.