Unlocking the Cause of Inflammation

For years the question was "why do those who are overweight (or obese) have a higher risk to their health than their lean counterparts?"

It was believed that the excess weight itself was the problem - greater demand on the whole body system to support the higher weight and maintain mobility of a heavier body.

In the last decade our understanding of the many things contributing to that higher risk have evolved and developed. As if on a collision course within itself, the body system - with ever increasing fatness - seems to turn on itself when the delicate balance between "health" and "illness" is tipped: insulin resistance, high blood sugars, hypertension, dyslipidemia, hyperinsulinemia, and inflammation - errupt and cascade in a domino effect leading to our worst health problems - diabetes, cancer, and heart disease.

But, as I noted in an article last week, it is not just the overweight and obese who get snagged in this domino effect of health ills - those who are considered normal weight - lean - can find themselves in the same boat as those who are much heavier. Being thin, it seems, does not automatically confer protection against long-term health problems.

This has led researchers to dig deeper to understand what is happening and why. The most recent addition on the list of potential warning signs of impending health problems is waistline circumferance and waist-hip ratio. These two measures offer warning to the lean that they may be developing "central adiposity" - that is belly or middle-torso fatness - even when they're normal weight and slim.

As reported by the USDA Agricultural Research Service this month - Inflamatory News about Fat Cells - scientists have uncovered why "fatness" - not simply overweight and/or obesity - matters. Researchers from the Obesity and Metabolism Laboratory, at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts identified key mechanisms in fat cells that cause chronic low-level inflammation in the body.

Deep within bone marrow, spleen, and lymph nodes lie a form of large white blood cells. As part of the immune system, these “macrophages,” as they are called, circulate within blood to seek out and devour bacteria, other foreign invaders, and cellular debris. Scientists have known that macrophages also appear in adipose, or fat, tissue. But their role in the tissue was once thought to be inconsequential.

Now, a new study explains important aspects of these immune cells in body fat, such as why they infiltrate, how they function, and just where they gather.

A number of researchers in the past few years have 'red flagged' inflammatory markers as one more marker to measure when assessing an individuals risk for heart disease or diabetes. This is because inflammatory markers like C-Reactive Protein are repeatedly observed in those with heart disease, cancer and diabetes. How the inflammation develops and continues to increase in the body has remained largely unknown.

This study shows that more than 90 percent of the macrophages in adipose tissue of obese mice and humans are located around dead fat cells. As the fat cells get bigger within fat tissue, the prevalence of macrophages increases proportionally. These new findings may partly explain the mechanisms inside the adipose tissue that cause the cells to secrete the inflammatory chemicals. These immune cells appear to be rushing to fat cells after their death to mop them up. When this happens, the macrophages may emit potentially dangerous amounts of inflammatory chemicals.

“When fat cells die, macrophages surround the dead lipids the same way white cells surround a wooden splinter in your skin,” Greenberg says. “The immune system is essentially surrounding and sequestering the dead fat cells and gorging on the leftover lipids and cellular debris.”

The macrophages identify the leftover insoluble lipid droplets as foreign bodies. In a case of molecular rescue gone awry, the findings may explain how enlarged fat cells, as found in obesity, promote obesity-related complications such as arthritis, insulin resistance, diabetes, or heart disease.