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For many, the discovery of a so-called fat gene begs the question: “Do these genes make me look fat?” Around the holidays, when sweet temptations abound, one has to wonder: “If my genes are going to make me fat anyway, why not indulge?”
But before you leap for the next plate of goodies, you’ll want to hear what panelists said at the Genetics and Public Policy Center’s Genetics Perspectives On Policy Seminar (GenePOPS), “Do These Genes Make Me Look Fat? Genetics, Environment, and Obesity.” The seminar was hosted December 5 at the National Press Club.
Moderated by the Center’s deputy director, Joan Scott, the panel included Bruce Blumberg, associate professor of the Department of Developmental and Cell Biology at the University of California, Irvine, who spoke on the effect environmental hormone disruptors may have on the body’s fat production and metabolism. Michael Christman, professor and chair of the Department of Genetics and Genomics at Boston University’s School of Medicine, shared his discovery of an obesity-causing gene variant, the so-called “fat gene,” and summarized the general impact of genes on obesity. Finally, Sally Squires, syndicated Washington Post health columnist, revealed her insights into how the public digests the often confusing and sometimes contradictory information about obesity dished up by the media.
The Centers for Disease Control (CDC) reports a significant increase in obesity rates in the United States over the last 20 years. Today, an estimated 65 percent of adult Americans are considered overweight; a whopping 30 percent are obese. Among children, obesity has tripled since 1980. Diabetes and other weight-related health problems are on the rise, affecting both individuals’ health and public health policy — New York City recently banned the use of trans fats in city restaurants. But while much of the focus has been on the highly visible culprits of rich Western diets and increasingly inactive lifestyles, new research sheds light on long-unknown factors in obesity: genetics and environmental toxins.
Fat Genes
Christman described the genetics of obesity and the contribution his recently discovered “fat gene” may play in the ongoing epidemic.
Obesity is a complex disease, Christman reminded the audience. Complex diseases, which account for many of the world’s ills, are thought to arise from the interaction of multiple gene variants with environmental factors, including diet, environmental toxins, and behavior.
The Human Genome and Hap Map Projects have set the stage for genome-wide association studies that aim to elucidate the roles gene variants play in complex diseases. Christman’s lab conducted just such a study looking for gene variants associated with obesity. Scanning some 100,000 genetic variants in a population of 1,500 people, Christman found a gene associated with increased body mass index—a discovery he purports to be the very first of its kind. Not surprisingly, the variant is quite common, occurring in about 10 percent of the world’s population.
But does the gene make you look fat?
Yes and no. Christman’s work shows that inheritance of the gene variant from both parents modestly increases the risk of obesity, but not everyone who has two copies of the gene is fat, and not everyone who is fat has two copies of the gene. Recently his team also discovered a “skinny gene” that appears to lead to a significantly lower average body mass index in the small portion of the population that has it.
Environmental Obesogens
According to Bruce Blumberg, obesity is more a symptom than a disease— just one element of a spectrum of disorders loosely defined as metabolic syndrome. Metabolic syndrome includes general obesity, central obesity (fat around the abdomen), atherogenic dyslipidemia (high “bad” cholesterol, low “good” cholesterol, and high triglycerides), high blood pressure, insulin resistance, and a tendency to develop blood clots. “In all,” said Blumberg, “this [metabolic syndrome] gives you a predisposition to type 2 diabetes, which is rampant, and cardiovascular disease.”
Blumberg’s research focuses on a subset of endocrine disruptors known as organotins. Endocrine disruptors are compounds that mimic or block the signaling of hormones such as insulin, testosterone, and leptin. Hormones play a central role in fat metabolism and maintaining the body. Leptin, for example, is a hormone that tells the brain when we are full and to stop eating. Some endocrine disruptors, known as obesogens (obese-generating), can interfere with the body’s biochemistry and actually can increase fat production.
Tributyltin chloride, or TBT, is “the most famous endocrine disrupting compound you’ve never heard of,” said Blumberg. But perhaps you should. Blumberg’s research shows that TBT, in addition to bizarre effects such as sex reversal in fish, causes prenatally exposed mice to increase fat production. At birth these mice have reduced body weights, but by maturity they are 10-15 percent heavier than controls—even when there is no subsequent exposure to TBT.
In the environment, TBT is ubiquitous. Originally used in marine paints to keep barnacles from cluttering ship hulls, TBT now is used in fungicides, as a wood preservative, and in the manufacture of PVC plastics, which are used to make water pipes and food packaging.
Although a causative effect has yet to be established, production of industrial chemicals in the United States, including TBT, closely parallels the obesity epidemic.
Blumberg cited a limited study that pegs the average human TBT blood concentration at 27nM, or just slightly higher than what Blumberg has shown to affect laboratory animals. While hardly an indictment of TBT as the source of the current obesity epidemic, it certainly warrants further exploration of TBT and other endocrine disruptors as possible contributors.
“Nutritional fog”
While the extent to which genes and endocrine disruptors contribute to obesity is unclear, one fact remains: Obesity is on the rise worldwide. The future may see the development of “intelligent” drugs that control fat genes and/or measures to protect the population from fat-inducing toxic chemicals, but in the meantime, balanced nutrition and adequate physical activity may be the only options for ensuring a healthy weight.
Sally Squires founded the Lean Plate Club, a syndicated Washington Post column, in July of 2001 to relay the latest health science news to the broader public and to address what she sees as widespread confusion about health and nutrition—something she described as “nutritional fog.” In addition to writing her column, she hosts a weekly Web chat forum to address specific concerns about diet and exercise.
An outgrowth of her column is the Lean Plate Club’s Holiday Challenge, a program aimed to help people avoid gaining weight over the holiday season. A study of NIH employees showed that non-overweight people gain less than a pound on average over the holidays, then lose it in the spring, but overweight people tend to gain more during this time and keep the extra weight. Over time, this can lead to or exacerbate obesity. The goal of Holiday Challenge participants is to weigh the same on January 1st as they did the day before Thanksgiving. Through the duration, Squires offers nuggets of advice on how to meet that goal through healthy choices.
“We really see this as a combination of journalism, of public health, and of public service,” she said.
Audience Reaction
The presentations fueled several questions from the capacity crowd.
Questions included what ways new research might impact individual’s daily activities: Will it motivate people to stay healthy, or dissuade them from adhering to a healthy lifestyle by making them feel powerless over their own physiques? Is surgery a viable option for controlling weight, or just another passing trend? Will the discovery of a skinny gene stimulate research into revolutionary diet drugs? Is obesity fed by food addictions? Will diagnostics play a role in managing the disease, or does the ability to detect fat genes in the absence of specific therapies simply add confusion? How are tax dollars best spent to treat the obesity epidemic?
The panelists’ consensus was that future obesity treatments and attitudes likely will be as complex as the disease itself. There is no single cause but a combination of factors working together. Likewise, the obesity cure is unlikely to come in the form of a magic bullet.
Christman explained that each individual has a genetically pre-determined weight range. Where they fall within that range ultimately is determined by that individual’s environment: what they eat, their behavior, and toxins present in their environment. Genetic contributions are real, he added, but individually they are all likely to be very modest. “If there were a huge risk from an individual gene, we’d have already found it,” he maintained.
Squires supported Christman’s assessment, citing the National Weight Control Registry, a list of people who have lost 30 pounds or more and kept it off for at least one year. The registry is proof that people are not biologically fated to a certain body mass index, she said.
The panel unanimously urged caution in flocking to easy fixes — “too good to be true” weight loss strategies usually are. Squires mentioned the challenges her column faces countering the unsubstantiated claims of trend diets. Even gastric bypass surgery falls short of guaranteeing long-term weight loss since, she said, people are finding “ways of bypassing the bypass.” Failing to adopt healthy habits, surgery recipients again risk developing obesity-related health problems as their weight creeps back up.
Emergence of gene testing for obesity is likely, despite the absence of any useful application. According to Christman, “there is a kind of a danger area because studies show that people want to be tested. They don’t care that there’s nothing you can do.” Asked if he thought there was a market for such a test, he answered emphatically yes.
Like maintaining a healthy weight by adopting a range of healthy habits, society’s response to the complex obesity epidemic must be multi-pronged and long term. Citing World Health Organization statistics, Squires said weight-related illnesses now are overtaking infectious diseases as the leading cause of morbidity and mortality worldwide. “We’ve got to get our arms around it,” she concluded.
Read the transcript of the event
Christman's slides
Blumberg's slides
Video Link:
http://www.dnapolicy.org/video/genepops/120506/index.htm
