Category Archives: Transhuman News

Researchers at Duke University have identified a protein that may help determine whether a person will develop an apple- or pear-shaped body, which could point to his or her risk of diabetes or heart disease.

In the study, published Monday in the journal Proceedings of the National Academy of Sciences, scientists analyzed zebrafish with and without the Plexin D1 gene, and found that those missing the gene had less visceral fat and were less likely to develop insulin resistance, a precursor of diabetes, even after eating a high-fat diet, according to a news release. A study published in February in the journal Nature also linked Plexin D1, among dozens of other genomic hotspots, to waist-to-hip regulation.

Heart disease is tied to greater visceral fat accumulation in the belly, or an apple-shaped body, compared to subcutaneous fat accumulation in the hips and thighs, which are characteristics of pear-shaped bodies. Fat concentration in the midsection is thought to induce inflammation and trigger metabolic diseases including high blood pressure, stroke and diabetes.

"This work identifies a new molecular pathway that determines how fat is stored in the body, and as a result, affects overall metabolic health," senior study author John F. Rawls, associate professor of molecular genetics and microbiology at Duke University School of Medicine, said in the news release. "Moving forward, the components of that pathway can become potential targets to address the dangers associated with visceral fat accumulation."

Rawls and postdoctoral fellow James E. Minchin studied the zebrafish because they found that mice died when they knocked out the Plexin D1 gene. According to the news release, the zebrafish were easy to study because they are transparent for most of their lives, so researchers could visualize fat distribution differences between those that contained the gene and those that were genetically engineered to lack it.

Scientists used a chemical dye that fluorescently stained the animals fat cells, which indicated that the mutant zebrafish had less visceral fat than those that still contained the Plexin D1 gene. Researchers also observed that those without the gene had visceral fat tissue composed of smaller but more numerous cells a factor known to reduce the risk of metabolic disease in humans compared to the fish that still had the gene.

After study authors fed the fish a high-fat diet for a few weeks, they saw even stronger differences of fat distribution between the groups of fish. When they gave the fish glucose, the genetically modified fish also cleared sugar from their bloodstream more efficiently, which in humans points to a reduced risk of diabetes and heart disease. Researchers at the Karolina Institute in Sweden analyzed human patient samples and similarly discovered a link between elevated Plexin D1 levels and a greater risk of type 2 diabetes.

"We think that Plexin D1 is functioning within blood vessels to pattern the environment in visceral fat tissue," Minchin, who was lead author of the study, said in the news release. That is, the genes that build blood vessels are also setting up structures to house fat cells. And this role skews the distribution and shape of fat in one direction or another. It is probably just one of many of different genes that each contribute to overall body shape and metabolic health."

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Gene may influence body shape, metabolic disease risk, study finds

IMAGE:Yellow coloring highlights the location of fat cells in this pair of zebrafish. In the adult fish at the top, which is about 10 mm, fat is deposited throughout the... view more

Credit: James E. Minchin

DURHAM, N.C. - Scientists have known for some time that people who carry a lot of weight around their bellies are more likely to develop diabetes and heart disease than those who have bigger hips and thighs. But what hasn't been clear is why fat accumulates in different places to produce these classic "apple" and "pear" shapes.

Now, researchers have discovered that a gene called Plexin D1 appears to control both where fat is stored and how fat cells are shaped, known factors in health and the risk of future disease.

Acting on a pattern that emerged in an earlier study of waist-to-hip ratios in 224,000 people, the study, which appears March 23 in the Proceedings of the National Academy of Sciences, found that zebrafish that were missing the Plexin D1 gene had less abdominal or visceral fat, the kind that lends some humans a characteristic apple shape. The researchers also showed that these mutant zebrafish were protected from insulin resistance, a precursor of diabetes, even after eating a high-fat diet.

"This work identifies a new molecular pathway that determines how fat is stored in the body, and as a result, affects overall metabolic health," said John F. Rawls, Ph.D., senior author of the study and associate professor of molecular genetics and microbiology at Duke University School of Medicine. "Moving forward, the components of that pathway can become potential targets to address the dangers associated with visceral fat accumulation."

Unlike the subcutaneous fat that sits beneath the skin of the hips, thighs, and rear of pear-shaped individuals, visceral fat lies deep within the midsection, wedged between vital organs like the heart, liver, intestine, and lungs. From there, the tissue emits hormones and other chemicals that cause inflammation, triggering metabolic diseases like high blood pressure, heart attack, stroke, and diabetes.

Despite the clear health implications of body fat distribution, relatively little is known about the genetic basis of body shape. A large international study that appeared in Nature in February began to fill in this gap by looking for regions of the human genome associated with a common metric known as the waist-to-hip ratio, which uses waist measurements as a proxy for visceral fat and hip measurements as a proxy for subcutaneous fat. The researchers analyzed samples from 224,000 people and found dozens of hot spots linked to their waist-hip ratio, including a few near a gene called Plexin D1 which is known to be involved in building blood vessels.

Rawls and his postdoctoral fellow James E. Minchin, Ph.D., were curious about how a gene for growing blood vessels might control the storage and shape of fat cells. When they knocked out the Plexin D1 gene in mice, all of the mutant animals died at birth. So they turned to another model organism, the zebrafish, to conduct the rest of their experiments. Because these small aquarium fish are transparent for much of their lives, the researchers could directly visualize how fat was distributed differently between animals that had been genetically engineered to lack Plexin D1 and those with the gene still intact.

By using a chemical dye that fluorescently stained all fat cells, the researchers could see that the mutant zebrafish had less visceral fat than their normal counterparts. They also noticed that the shape or morphology of the fat cells themselves was different. The zebrafish without the Plexin D1 gene had visceral fat tissue that was composed of smaller, but more numerous cells, a characteristic known to decrease the risk of insulin resistance and metabolic disease in humans. In contrast, their normal siblings had visceral fat tissue containing larger, but fewer fat cells of the kind known to be more likely to leak inflammatory substances that contribute to illness.

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New gene influences apple or pear shape, risk of future disease