Visceral fat linked to heart attacks, strokes

By Terri Coles

TORONTO (Reuters) - We already know that having a beer belly is bad for your heart. Now, we might also know why.

New research shows a direct link between inflammation around deposits of visceral fat, or fat that forms around major organs in the stomach, and atherosclerosis, the process of artery hardening that can lead to blood clots, heart attacks and strokes.

The research team, led by Dr. Daniel Eitzman, a cardiologist at the University of Michigan Cardiovascular Center, also discovered that a class of drugs commonly given to diabetics reduced inflammation, an abnormal response where the body attacks its own tissue, and halted artery hardening.

Human applications are still a long way off, but the results, published this week in the medical journal Circulation, may help reveal more about why the link between inflammation and atherosclerosis exists, how it can be treated, and if a simple blood test might one day indicate heart risk before other risk factors show up.

The scientists first discovered the link by accident, Eitzman said. They were studying the production of leptin, a hormone related to appetite, metabolism and fertility, in mice by transplanting fat cell clusters from normal mice into mice lacking the gene for leptin production. The absence of leptin makes mice infertile and obese. The fat-transfer operation promoted leptin production in the host mice, which reduced their infertility and obesity, but it also resulted in chronic inflammation around the transplanted clusters.

"When we went on further to analyze the fat transplant," Eitzman said, "We found that the transplants developed chronic inflammation, and that the characteristics of this inflammation were very similar to those that had been previously described in fat in humans, and in animal models, that occurs with severe obesity."

The inflammation in the mice that received fat implants was unexpected, Eitzman said, because the mice were genetically the same but for the leptin gene. The inflammation had to be directly related to the fat, he said, because it was transplanted, which ruled out factors like overfeeding or diabetes and its associated metabolic problems, he said. "This model is not a diabetic model, so it shows that you don't need that diabetes to get that vascular risk."

Because normal mice don't experience artery-hardening, Eitzman and his team studied a strain of the animal bred to have a genetic disposition towards atherosclerosis and high cholesterol by dividing them into three groups: one that got implants of visceral fat from normal mice, one that got implants of subcutaneous fat -- the kind found just under the skin -- from normal mice, and another that underwent the transplant operation without actually receiving the fat transfer.

They tested for blood sugar and hypertension in the mice to make sure they were normal.

They found that the mice with visceral fat transplants developed hard arteries much more quickly than normal -- including in arteries far from the transfer site -- and showed the same type of inflammation as the leptin-deficient mice. The mice with subcutaneous fat implants had increased inflammation without increased atherosclerosis, while the mice without implants had no hardened arteries or inflammation. This showed, Eitzman said, that there seemed to be some interaction between inflammation in the visceral fat and atherosclerosis.

The researchers were then able to treat the mice with pioglitazone, a drug in the thiazolidinedione (TZD) class that's given to diabetics. The mice with visceral fat transplants saw improved inflammation and atherosclerosis with TZDs, but the other mice were not affected. The researchers plan to look at other classes of drugs known to reduce inflammation, like statins, to see if they can have a similar effect, Eitzman said.

They are also investigating further to identify the factors that may trigger macrophages, which lead to inflammation, as well as any biomarkers that may show up in blood tests to indicate a risk for atherosclerosis. If doctors knew which markers of inflammation to look for, a simple blood test could be used to identify people who may be at risk for atherosclerosis later, Eitzman said.

In the meantime, the advice for anyone who wants to reduce their risk of visceral fat-related health problems is the same, Eitzman said: lose weight through healthy diet and exercise. "With weight loss you're going to lose not only total body weight but also visceral fat," he said. "It's probably the case that weight reduction is going to reduce these inflammatory characteristics of the visceral fat."

That applies not just to people who are overweight or obese, but to anyone who has a high waist-hip circumference ratio. Previous studies have shown that these individuals may also be at risk for health problems like atherosclerosis and diabetes, even if they are at a normal weight. A Canadian study released last year showed that people of Chinese and South Asian ancestry tended to have more visceral fat compared to those of European ancestry.

"I think that this goes beyond body mass index," Eitzman said, "and there are people that may be classified as even normal weight that are still going to have inflammatory fat."