When good cells go bad by the fat company they keep
January 2, 2007
ANN ARBOR, Mich.---Macrophages are normally good cells and key players in the immune system to fight off foreign invaders. But when a macrophage is presented with a high-fat diet, that cell starts to protest by causing inflammation.
These macrophages are present in everyone—they are the white cells that normally fight off infections. Researchers at U-M's Life Sciences Institute have found that in the company of high-fat diets and obesity, they travel to the fat tissue and behave badly.
Scientists have known that obesity increases the risk for heart disease and diabetes, but no one fully understands what cells are involved in this process. Dr. Carey Lumeng from the Department of Pediatrics, researcher Jennifer L. Bodzin, and Alan Saltiel, LSI director, have discovered that the very obese and diabetic mice have large numbers of macrophages in their fat that are activated to promote inflammation.
"It's almost like the macrophages are responding to inflammatory signals in the fat tissue," said Dr. Lumeng. "These macrophages may be a central cause of diabetes because they communicate with the fat cells and alter their function in a way that leads to insulin resistance."
The new study featured on the cover of the Journal of Clinical Investigation with an accompanying commentary links obesity, inflammation and diabetes to macrophages. Although macrophages are found in the fat tissue of lean and obese animals and humans, scientists don't understand how they function in these settings. The new paper shows that the fat tissue macrophages can actually change their properties. In lean mice, the macrophages may naturally protect the fat cells and maintain their normal function, but in obese mice, they change and cause inflammation, contributing to the development of obesity-associated diseases.
Importantly, the study shows that a factor called interleukin 10 (IL10) is produced by the macrophages under lean conditions, but not in obese conditions.
"IL10 has been correlated with better diabetes control in patients and we show that it is made by macrophages in fat under lean conditions, and seems to protect adipocytes so they keep responding to insulin," said Dr. Lumeng. "using interleukin 10 or finding ways to make it work better has potential as a novel way to target the inflammation in diabetes."
The paper "Obesity induces a phenotypic switch in adipose tissue macrophage polarization" by Carey N. Lumeng, Jennifer L. Bodzin, and Alan R. Saltiel appeared as the cover story in the Journal of Clinical Investigation January 2, 2007.
