The quest to find a pharmaceutical cure for obesity may have just taken one big step forward.
Researchers at the University’s Life Sciences Institute, under Director Dr. Alan Saltiel, recently discovered that suppressing a particular gene called IKKE in mice conveyed resistance to the effects of a high-fat diet.
IKKE, also found in humans, encodes for a protein kinase, which turns on and off other proteins in a cascade pathway. The kinase is ultimately responsible for regulating the metabolic genes that can cause obesity. The study found that deletion of IKKE — a so-called “obesogene” — and its associated protein kinase boosted metabolism in mice.
According to the Centers for Disease Control and Prevention, an estimated 34 percent of U.S. adults aged 20 and older were obese in 2008, with 32 states having a prevalence greater than or equal to 25 percent.
Fed a fat-enriched diet for three months over the course of the study, mice without IKKE gained little weight compared to those with IKKE, which were later declared obese. Preliminary differences in the low-grade inflammatory responses, which characterize obesity, were seen as soon as six weeks into the study.
Unlike previous genetic markers linked to obesity, IKKE has thus far been the first to largely negate the effects of diet.
Dr. Shian-Huey Chiang, an assistant research scientist in the lab and an author of the study, said she initially planned to study insulin signaling in context of diabetes.
Chiang said she worked with the family of genes collectively known as IKK and sought to study its role in glucose uptake and insulin resistance.
“In the past 10 years, lots of studies have shown that inflammation is associated with diabetes,” she said. “People used to think that obesity just jumped to diabetes, but they didn’t know what happened in between.”
What Chiang and her colleagues found instead was a definitive link between one particular gene from the IKK family and obesity in mice.
“We were expecting them to gain weight like the control mice and see the progression of insulin sensitivity, but instead we saw little change in body weight,” Chiang said. “For them, it was like having McDonald’s everyday for three months.”
Chiang said the serendipitous finding will no doubt spark further research into the powers of the protein kinase.
Previous studies have shown that mice with disabled IKKE were also more susceptible to viral infection, illustrating the gene’s potential role in mounting an immune response.
“To stay lean, this is a bad gene to have, but for protection against viral infection it’s great,” Chiang said.
The complex pathway underlying the gene’s expression, consequently, is still a deterrent for pharmaceutical companies to develop IKKE protein kinase inhibitors, she said.
However, pharmaceutical development of kinase inhibitors is already under way and a drug against obesity may be viable, Chiang said.
“Gene suppression could help with energy expenditure, but staying on a healthy diet and exercising is still going to be key,” Chiang said.