Stanford University School of Medicine researchers have found that macrophages, the scavenger cells of the body's immune system known as troublemakers for their role in obesity, may sometimes be beneficial for metabolism.
The new finding is based on a study that highlights the beneficial role of macrophages in combating the effects of a high fat diet in mice.
"Macrophages have a reputation for being the bad guys. We have found that they can also do good things," Nature magazine quoted senior study author Dr. Ajay Chawla, Assistant Professor of Medicine, as saying.
The study led to the identification of a molecular switch that can shift the called into the more desirable mode, a finding that could play a role in blocking the development of insulin resistance and type-2 diabetes seen with obesity.
The researchers bred genetically engineered mice that did not have the PPAR-gamma molecule, which has been implicated in how cells detect fatty acids, the building blocks of dietary fat.
It was found that simply missing PPAR-gamma in macrophages caused mice to gain about 20 per cent more weight than their normal counterparts, and predisposed them to the development of diet-induced insulin resistance.
"We predicted that the inflammation might be higher and there might be insulin resistance, but it was a surprise that the mice actually gained weight," said Chawla.
Researchers say that macrophages are lost in the case of excess fat consumption, and those lost are specifically the ones that undergo the alternative activation program.
"When you lose these cells, the adipose tissue can't deal with incoming lipids properly, and the mice become fat as well as glucose intolerant and insulin resistant. Basically when the system gets overwhelmed, the reparative responses get overwhelmed as well," said Chawla.
"These findings are especially exciting because other research has recently shown the same differences in macrophage activation in humans," said Justin Odegaard, an MD student in Chawla's lab.
He says that the fat reserves of obese people have been found to contain inflammatory macrophages, while those of lean people contain anti-inflammatory macrophages, replicating the observations made in their animal model.
Previous research had also shown that when people lose a lot of weight, the profile of their macrophages changes, shifting to the anti-inflammatory mode. In the present study, the researchers have identified a molecular switch.
They believe that their work raises the possibility that existing anti-inflammatory therapies might be targeted at adipose tissue macrophages to treat obesity and insulin resistance.