21st Century Obesity Pandemic Still Suffering From Effects of Tuberculosis Plague of the 1800s

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Unlike our ancestors, we are faced with an abundance of food and our bodies store excess fat that triggers a pro-inflammatory response in systems that evolution created to handle microbial threats

Manhasset, NY (Vocus) June 24, 2009

Modern humans are a long way from starvation or pandemic infectious diseases like tuberculosis that took the lives of a billion people. But the body's banking system that deposits calories in the event of famine or acute infection is continuing to respond as it did in olden times. Jesse Roth, MD, a diabetes and obesity researcher at The Feinstein Institute for Medical Research, has identified a link between tuberculosis and the metabolic and inflammatory processes that is tied to obesity. In an intriguing commentary in this week's Journal of the American Medical Association (JAMA), Dr. Roth explains how the modern body has evolved to handle this banking problem - and why it was favorable to human health more than 100 years ago but bad for human health today.

"Unlike our ancestors, we are faced with an abundance of food and our bodies store excess fat that triggers a pro-inflammatory response in systems that evolution created to handle microbial threats," said Dr. Roth. "People who are obese have more pro-inflammatory forces going on. This is a carry over from 100 years ago when tuberculosis was much more of a continuing threat and food supplies were scarce." The result, he said, is an increase in inflammatory diseases such as diabetes, heart disease and stroke. "We've come to the 21th century where starvation and tuberculosis are not a threat but we have maintained the same `body' set as our ancestors," he said.

Dr. Roth is an expert on diabetes and obesity. Now, he's trying to identify ways to tame the pro-inflammatory processes of the body associated with diabetes and obesity.

"We now believe that many of the complications from obesity and diabetes are due to these inflammatory processes," explained Dr. Roth. There is growing evidence that people who are obese have a pro-inflammatory program that is more active than necessary for defense. And in the absence of microbial invaders (like tuberculosis), the body is using up resources (by arming itself for defense), and this pro-inflammatory response can result in damage to cells and molecules of the body, he said.

Dr. Roth explained that so-called "thrifty" genes evolved because the body works hard to conserve calories (as a source of energy). This energy bank account comes to good use during times of famine and infection. During starvation, the body needs energy from the stored fat cells that it can't get from food. During infection, the body needs energy to rally up immune defenses to fend off disease.

The balance between the calorie savings to prevent starvation and calorie expenditures to fight microbial invaders was upset by the tuberculosis pandemic during the 18th and 19th centuries. Tuberculosis was the leading killer of young adults. Once infected, people retained live bacteria even when they were seemingly recovered; bacteria could reinvade whenever the defenses of the body were down. These times included periods of starvation, illness and old age. The presence of the TB infection led to evolutionary forces that caused a shift in the body's budgeting of calories. More calories were spent on defense at every level of calorie banking.

The pro-inflammatory responses that go hand-in-hand with the large calorie stores intrinsic to modern obesity is a vestige of another era, Dr. Roth said. "What was very beneficial for our ancestors is detrimental to us today. This harmful response is magnified by the ready availability of food. This abundance of food leads to an even greater pro-inflammatory response.

Fat comes in two kinds. There is subcutaneous fat stored under the skin. This is a simple bank account for fat and carries few pro-inflammatory molecules. By contrast, fat cells can also be deposited viscerally inside the abdominal cavity. What's more, these fat cells also recruit macrophages, immune system scavenger cells that express a powerful pro-inflammatory program, and release pro-inflammatory molecules called cytokines. When people gain extra weight, most of the calories go into the visceral bank account. Weight loss also reduces fat cells in the visceral organs.    

Whenever we deposit fat, the body makes a decision where it should go. Dr. Roth and his colleagues suspect that there are switches that control the travel routes that deposit fat cells. "If we could manipulate the address of the fat cells, we could reduce the level of damaging pro-inflammatory responses," he said. The idea would be to send fat cells to the subcutaneous regions. That would reduce the pro-inflammatory response. But it could also result in even heavier bodies. Dr. Roth said that medicines would have to be designed with a one-two punch: to bypass the visceral fat stores and help reduce the burden of fat cells on subcutaneous tissue.

What are the implications for today's society? "We know that exercise, even in moderation, acts to turn down the pro-inflammatory response," said Dr. Roth. "Very modest weight loss (five percent or less) is also an effective way to lower this damaging pro-inflammatory response."

Scientists at the Feinstein Institute are actively developing drugs that target the body's pro-inflammatory responses and could ultimately be tested for its benefit in protecting against the damaging effects of obesity and diabetes.

While these responses are disadvantageous in the U.S. and other parts of the industrialized world, they may still be of benefit for people in countries where tuberculosis is common and food is scarce.

About The Feinstein Institute for Medical Research
Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in cancer, leukemia, lymphoma, Parkinson's disease, Alzheimer's disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, neuroimmunology, and medicinal chemistry. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient, annually enrolling some 10,000 subjects into clinical research programs

Contact: Jamie Talan, science writer-in-residence
516-562-1232 (w) or 631-682-8781 (c)

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