"More importantly", notes Long, "when we did metabolic studies, we found that the animals with the active Hedgehog pathway not only were leaner, they also had lower blood glucose levels and were more sensitive to". But the mice that had been engineered with genes to activate the pathway did not gain any more weight than did control animals that consumed normal diets.
The research appears in the journal eLife. The authors quoted in their paper, Here by inducing expression of constitutively active Smoothened (SmoM2) or Gli2 (ΔNGli2) in the adipocyte lineage of postnatal mice, we show that targeted activation of Hh signaling suppresses high-fat-diet-induced obesity and improves whole-body glucose tolerance and insulin sensitivity. The Washington University team focused on the pathway specifically in fat cells, engineering mice with genes that activated it in those cells when they ate a high-fat diet.
As it turned out, stimulating the hedgehog pathway inhibited the size of the fat cells, said senior investigator Fanxin Long, Ph.D., a professor of orthopedic surgery at Washington University.
"Fat gain is due mainly to increased fat cell size", researcher Fanxin Long said in a statement from the school.
After eight weeks of eating the high-fat diet, control animals whose Hedgehog pathways had not been activated became obese.
The method, which stops fat cells from growing larger, targets a common cause of obesity in adults. This can lead to weight gain and obesity - which is a risk factor for, and some types of. Specifically, it prevented the cells from collecting and storing fat droplets. The researchers feel that if they can figure out strategies to carefully target fat cells then activating the pathway could be helpful in fighting obesity. "Each fat cell grows bigger so that it can hold larger fat droplets".
A new way to fight obesity?"We gain weight mainly because fat cells get bigger, as opposed to having more fat cells".
To explore if Hedgehog signaling also has an effect on diet-induced obesity after birth, Long and his team genetically engineered mice so that the Hedgehog pathway in fat cells would activate when they ate a high-fat diet.