Apple or pear? Gene may decide body shape

Scientists have identified a gene that may decide whether a person will develop an apple- or pear-shaped body.
It is known 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.
It has not been clear why fat accumulates in different places to produce these classic "apple" and "pear" shapes.
Now, researchers at Duke University have discovered that a gene called Plexin D1 appears to control both where fat is stored and how fat cells are shaped.
The new study, published 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, senior author of the study and associate professor of molecular genetics and microbiology at Duke.
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.
An international study that appeared in journal Nature last month looked for regions of the human genome associated with a common metric known as the waist-to-hip ratio.
The researchers analysed 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 were curious about how a gene for growing blood vessels might control the storage and shape of fat cells.

They experimented on zebrafish which are transparent for much of their lives and researchers could directly visualise 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 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.

Collaborators at the Karolinska Institute in Sweden analysed human patient samples and showed that levels of Plexin D1 were higher in individuals with type 2 diabetes, suggesting it may play a similar role in humans.