Dr. Christopher Still has researched obesity at Geisinger for nearly 30 years. He’s seen a high prevalence of obesity and what he calls “its comorbid medical problems or complications” in his Central Pennsylvania patient population.
“As our body mass index goes up, as we become heavier, the prevalence of these comorbid medical problems, such as diabetes, sleep apnea, fatty liver disease, high blood pressure, cholesterol, increase as well," said Still, who works as the director for Geisinger’s center for obesity and metabolic research and as a professor at the Geisinger Commonwealth School of Medicine.
"Because our BMI tends to be heavier in Central Pennsylvania, there's an increased prevalence of those disease states to not only manage clinically but also try to prevent and have treatment options for them,” he said.
Still co-authored research recently published in the national science journal ‘Nature’ using data from Geisinger’s genetic database, targeting a gene that could have implications for the treatment of obesity and cardiovascular diseases.
The research
The scientists studied data from more than a million patients in three continents for this paper using Geisinger's MyCode initiative, a genetic database. Through the initiative, patients consent to the use of their genetic information for research.
“We could not do this research without our patient participation in our MyCode initiative, because that's where we found patients allowing us to to use their genetic information,” Still said.
They found that people who have certain variants of the FNIP1 gene had lower liver fat levels, better blood sugar regulation and a healthier fat distribution. They found about 1 in 7,000 carry the mutated gene.
The mutations, while rare, protected individuals from the risk of the cardiometabolic diseases, with about 60% lower odds of developing cardiometabolic disease, which Still defines as, “a whole host of medical problems that patients have, similarly to diabetes, sleep apnea, fatty liver disease, high blood pressure, and they're really all associated with the disease of obesity. So cardiometabolic has to do with the heart and our metabolism.”
The FNIP1 gene deals with fat storage.
“It was usually associated with hunters and gatherers when food may have been more scarce. It helped us survive those rare times where they didn't have food. But now we have plenty of food, and it actually can exacerbate or make obesity and diabetes and heart disease worse in some individuals,” Still said.
This finding serves as a starting point for further obesity research and potential treatments.
“Our study implicates the FNIP1 pathway in human energy metabolism and highlights its inhibition as a potential therapeutic strategy in cardiometabolic disease,” the paper says.
Implications for obesity treatments
The state Department of Health reports that 33% of Pennsylvania adults and 18% of children K-12 are affected by obesity. Nationally, that prevalence is about 42% in adults and 19% in children.
The findings about the mutated gene could have implications for future treatment of obesity, according to Still.
“The implications would be that if we could know that this gene, if it's mutated, is beneficial. Someone could develop a protein to block this and make it more favorable, similar to the GLP-1 medications that are so prominent in today's society, for treatment of these comorbid medical problems,” he said.
He said this research was just step one in finding further treatments for obesity.
“There's a lot of testing and research that needs to be done, but it's very interesting that this is one area of genetics playing a part in our metabolism. If we can alter genetics, then I think down the road this could be a very fruitful target for these very prominent diseases,” Still said.
Still called these findings “a game changer” for cardiometabolic disease management.
“Obesity and cardiometabolic diseases are diseases. It's not a lack of willpower. It's not the patient's fault. A lot of people blame the patients or patients blame themselves, saying they're not working hard enough or I can do better," he said. "This once again proves the biology of the disease of obesity and its comorbid medical problems. This study just again emphasizes that it is not the patient's fault."
