Interviewee: Daniel Eitzman, University of Michigan
Apple or Pear?
Not all fat is created equal. Accumulating most of your fat around your waistline, or having what’s often called an “apple shape,” is known to be more dangerous than storing fat around your hips and buttocks, known as having a “pear shape.”
That’s because they are actually two different kinds of fat. The fat in your abdomen tends to be visceral fat, which builds up around your organs, as opposed to subcutaneous fat, or fat under the skin. Visceral fat is strongly linked to metabolic syndrome, the insulin resistance that increases our risk of heart disease, cancer, and all sorts of diseases associated with aging.
Obesity researcher Daniel Eitzman says that makes it tricky to study the effects of the fat itself.
“When we look at obese humans or animal models of obesity, they develop other well-established risk factors such as diabetes or elevated blood cholesterol that can affect heart disease,” he explains. “So it’s difficult to tease apart the specific role of the belly fat from these other associated risk factors that are triggered by obesity.”
But in a new study in mice, Eitzman and his team at the University of Michigan were able to control for those factors.
“This study demonstrates a direct effect of belly fat on, on heart disease, and this effect occurs without changes in diabetes or blood cholesterol,” Eitzman says.
The study come came about serendipitously, he says. The researchers were studying appetite hormones produced by fat by transplanting different kinds of fat from other mice into non-obese mice.
When they looked at the transplants several months later, they found fat cells had become inflamed in mice that received belly fat.
“It was very interesting to us that the inflammation in these transplanted fat pads looked very similar to the type of inflammation that is seen in humans with obesity,” Eitzman explains.
That led them to do fat transplantations in mice that are bred to have no diabetes or high cholesterol but are prone to heart artery blockages. Again, the researchers saw inflammation around fat cells only in the belly fat group.
“Mice that received this inflammatory fat developed a greatly accelerated amount of blockage in the arteries compared with other mice that received the same operation with no fat implantation, or with mice that received a different type of fat, subcutaneous fat,” says Eitzman.
And as they wrote in the journal Circulation they didn’t stop there.
“The next question we wanted to address was: ‘Is there any way we can reduce the fat inflammation, and if we do reduce the fat inflammation, will this have a beneficial effect on heart disease?’” Eitzman says.
“The reason we used it is, it has a particular effect on what the fat cell secretes, and this drug also affects inflammation,” Eitzman says. “So when we treated mice that received the fat transplantation with pioglitazone, this reduced the inflammation in the fat and also reduced the effect of this type of fat on the blockages in the arteries.”
“The jury is still out on the potential cardiovascular benefits of pioglitazone, but it’s possible that this drug, or drugs like this drug, may be particularly effective in reducing the cardiovascular risk associated with inflammatory fat,” he says.
But Eitzman thinks this line of research will lead to better, more specific drugs to protect against the effects of belly fat.
“The problem with pioglitazone is, while it is effective at reducing inflammation, it affects many other tissues, and many other molecules, and so there may be improved therapies if we gain a better understanding of what these specific factors are,” he says.
In the meantime, Eitzman says it’s yet another reason to get rid of that gut.
“I’ve always told patients to lose weight in attempt to reduce their risk for heart disease, but this study shows that we may even may need to be more aggressive,” he says.
“Even if the diabetes has been taken care of and the blood lipids look okay, if they still carry this excessive belly fat, there may be yet another reason to lose weight, and the weight loss may reduce inflammatory characteristics of this belly fat.”
Indeed, belly fat is dangerous even if you don’t qualify as obese. “The results of these studies may not only apply to the obese population,” says Eitzman.
“There are people who don’t meet criteria for obesity that still have excess belly fat, and these patients are likely also at increased risk for heart disease. There also may be obese patients with a pear-shape that are not at the same risk that other people are that carry this fat centrally,” he says. “Identifying what these specific factors are that mediate the risk of the different types of fat may be very helpful in designing therapeutic strategies to reduce the vascular risk associated with obesity.”
This research was published in Circulation, January 2008 and funded by the National Institutes of Health.
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