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Giant-eater cells key to fat-diabetes link

Sun, 12th Oct 2008

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Scientists have discovered the cellular culprit that causes obese individuals to develop diabetes.

A macrophage of a mouse forming two processes to phagocytize two smaller particles, possibly pathogensWriting in this weeks' Cell Metabolism, University of California San Diego researcher David Patsouris and his colleagues have found that an angry immune cell could be to blame.  Ironically the cells involved are macrophages, Greek for "giant eaters".  These are long-lived cells whose job it is to engulf and break down damaged and infectious material.  But in obese individuals, in this case mice fed the rodent equivalent of junk food, a population of the cells move into muscle and fat tissue around the body and interfere with the body's handling of glucose and its sensitivity to the sugar-regulating hormone insulin.

Now, in an elegant series of experiments, the team have identified a chemical marker, CD11c, which is present on the surfaces of just these errant macrophages.  This has enabled the researchers to selectively kill the cells by targeting them with the toxin made by diptheria bacteria.  When this occurs in obese mice the animals show immediate and dramatic improvements in insulin and sugar levels and also markers of inflammation significantly decrease.

This suggests, the team say, that the same trick might work in humans by using the marker they have identified to target this cell population, either with drugs to shut down or disable the cells. 

Exactly how the CD11c-positive macrophages are altering metabolism in this way for the moment remains a mystery, but one the researchers are hungry to get their teeth into solving.

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