Genes and obesity

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Thick or thin. Whichever you are, it may not be your fault.

HealthFirst reporter Leslie Toldo says our weight may boil down to a genetic link we share with mice.

Over half of us humans are overweight. That’s not really new, but for some, that extra fat may have more to do with destiny than lifestyle.

Lisa Bohner has one wish. “To have life again. To be normal.”

She and her 455 pounds struggle every step, every day. “Right now ... I only merely exist.”

But this nearly quarter-ton woman may share a genetic link with a one-ounce mouse.

“It’s a way that we can illustrate using mouse models with specific genetic characteristics to dissect these processes that are so common in the human population,” Dr. Philip Wood, DVM, PhD, said.

Wood created six mouse models in his lab, then inactivated fat-burning genes in each one. Some got fat. Others built up insulin resistance. Others stayed healthy.

Now, he’s matching each mouse with a two-footed counterpart—a person with the same genetic makeup. “We can sort of find the tipping point, if you will. When does obesity show up? When does diabetes show up? When does High Blood Pressure show up?”

The goal is to indentify people whose genes predispose them to being fat and all the diseases that follow, and find therapies to turn off those switches.

“The idea is that we’re then beginning to put together the pieces to eventually pursue an individualized medicine for the average obese, diabetic individual that comes in,” Wood said.

Wood says while diet, exercise and environment make up half of the obesity picture, genetics controls the rest, meaning Lisa can’t blame her weight entirely on her genes.

“I don’t ask for any miracles,” she said.

Not a miracle, but a genetic breakthrough that one day could lift her 455-pound burden.

Wood says he hopes to use the same mouse models that match human genotypes to test new drugs.

BACKGROUND: Some doctors call obesity the most prevalent, fatal, chronic, and relapsing disorder of the 21st century. It is a leading cause of mortality, morbidity, disability, health care utilization and costs in the U.S. Experts predict the increase in obesity will strain our health care system with millions of additional cases of diabetes, heart disease and disability. Obesity is a disease that impacts more than one-third of the adult American population, which is about 72 million people. More than 66 percent of adult Americans are categorized as being overweight or obese. Since 1960, Americans have increased average heights by 1 inch and average weight by 25 pounds. In 1963, a 10-year-old boy weighed about 74 pounds. Now, the average boy weighs 85 pounds, according to The Obesity Society. Each year, obesity causes about 112,000 excess deaths in America. Obesity is linked to many adverse health effects including High cholesterol, diabetes, hypertension, gallstones, fatty liver disease, sleep apnea, heart failure, birth defects, miscarriages and asthma. Health care costs of American adults with obesity amount to about $147 billion.

GENETIC LINK: The best success stories providing evidence for obesity genes come from several cases of extreme obesity due to mutations of single genes, according to the Centers for Disease Control. Melanocortin 4-receptor gene, which is related to the control of feeding behavior, has been found to be strongly associated with a minority of obesity cases in several populations. Progress in identifying the multiple genes associated with the most common form of obesity has been slow but is accelerating. Single mutations in 11 genes were strongly implicated in 176 cases of obesity worldwide, according to the CDC. Additionally, 50 chromosomal locations relevant to obesity have been mapped with potential causal genes identified in most of those regions.

Recently, studies reported that another gene called FTO, fat mass and obesity-associated gene, might be responsible for up to 22 percent of all cases of common obesity in the general population. This gene also shows a strong association with diabetes, according to researchers.

FOR MORE INFORMATION:

Deborah Robison, Director of Communications
Sanford-Burnham Medical Research Institute at Lake Nona
Orlando, FL
(407) 745-2073

Leslie Toldo
WJRT

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