Macrophages - the scavenger cells of the body's immune system - are known as troublemakers for the role they play in obesity, but Stanford University School of Medicine researchers have found that the cells can also be saviors when it comes to metabolism.
The researchers highlight the beneficial role of macrophages in combating the effects of a high-fat diet in mice in a study that will be published in the May 21 advance online edition of Nature. "Macrophages have a reputation for being the bad guys," said the study's senior author, assistant professor of medicine Ajay Chawla, MD, PhD. "We have found that they can also do good things."
Chawla and his colleagues have identified a molecular "switch" that can shift the cells 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.
"We have identified a previously unappreciated role that the macrophage can play in protecting against the deleterious effects of a high-fat, or 'Western,' diet," said one of the article's lead authors, Justin Odegaard, an MD/PhD student in Chawla's lab. The deleterious effects include obesity and insulin resistance, which put a person at higher risk for heart disease and type-2 diabetes.
"These results are very exciting because they challenge the typical view in the field of obesity research where investigators tend to think of the macrophage as a pathogenic cell in Western diet-induced obesity and insulin resistance," said Roberto Ricardo, the other lead author, who is also an MD/PhD student in Chawla's lab.
Macrophages once seemed an unlikely participant in obesity. They are white blood cells that swallow and digest cellular debris and pathogens, triggering other immune cells to aid in the response to a pathogen. But in recent years, macrophages found in fat tissue of obese animals have been fingered as the source of chemical signals that exacerbate the problems of obesity and insulin resistance that accompany eating too much fat.
In this villainous role, activated macrophages release chemical signals that trigger inflammation. The increased blood flow of inflammation is necessary for wound healing and clearing infections, but long-term inflammation interferes with normal cellular processes and leads to many of the chronic conditions that plague modern society, including heart disease, obesity and type-2 diabetes.
Chawla's group investigated the opposite effect - the macrophage's resolution of inflammation. They wanted to figure out what flipped the cells into that mode, known as alternative activation.
The researchers reasoned that an impairment in alternative activation might be the cause of the prolonged inflammation and insulin resistance. They focused on a molecule found in the nucleus of cells called PPAR-gamma, which has been implicated in how cells detect fatty acids, the building blocks of dietary fat.