Sci. Aging Knowl. Environ., 21 September 2005
Vol. 2005, Issue 38, p. nf75
[DOI: 10.1126/sageke.2005.38.nf75]


Plumbing Problem

Lymph system malfunctions might promote obesity

Mitch Leslie

For some patients, obesity could be a matter of bad drainage, a new study suggests. The work shows that mice with defective lymphatic systems amass fat. The results suggest a possible explanation for some cases of human obesity.

The lymphatic system sops up excess fluid from tissues and shuttles white blood cells around the body. Some evidence hints at a link between local fat buildup and lymphatic malfunctions. For example, in patients with lymph stagnation in an arm or leg, fat often accumulates in the limb. And preliminary work indicates that in the test tube, lymphatic fluid, or chyle, spurs immature fat-storing cells to grow up and start caching lipids. Developmental biologist Guillermo Oliver of St. Jude Children's Research Hospital in Memphis, Tennessee, and colleagues chanced upon a connection between lymphatic defects and widespread fat accumulation while they were studying a gene called Prox1, which orchestrates lymphatic system development. Most mice without two copies of Prox1 die. But some animals in one strain survive with only one copy. Oliver and colleagues noticed that these mice grew tubby with age, and they wanted to find out why.

Lymphatic system vessels of Prox1-deficient mice were misrouted or missing, and their abdominal lymph vessels sprang leaks. The mice also ballooned, outweighing normal animals by nearly 33%. Compared with control mice, the altered rodents harbored larger fat-storing cells, and some carried more of the containers. When the researchers deleted one copy of Prox1 from only the lymph system, the mice became corpulent. Together, the results suggest that lymphatic defects stimulate obesity in the mice, says Oliver. Because chyle spurs fat-storing cells to mature, the researchers conclude that leaking lymph vessels spur the fat accumulation. Quantities of the hormones insulin and leptin, which controls appetite and energy use, shoot up in obese patients, and they did the same in the Prox1-deficient mice. But the rise didn't begin until after the rodents had already begun to blimp out, Oliver notes, indicating that an oversupply of leptin and insulin is a consequence, not a cause, of fat buildup. Although eating too much and exercising too little account for most instances of obesity in people, some cases could stem from faulty lymph circulation, says Oliver. Researchers should check whether seriously overweight individuals harbor glitches in genes that shape the lymph system, he says.

The study is significant because it pinpoints an unexpected possible trigger for obesity, says endocrinologist Evan Rosen of Harvard Medical School in Boston. However, he's not convinced that lymph leakage itself underlies weight gain because it's not clear where the extra calories come from to make the mice fat. For example, he notes, before the altered mice grew hefty, they ate and exercised about the same amount as normal rodents did. Lymph might be inciting fat-cell maturation, but some other factor--such as slowed metabolism--is necessary to provide the fat to fill those cells, he says. Additional experiments should determine whether improving lymph circulation will pull the plug on obesity.

September 21, 2005
  1. N. L. Harvey et al., Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nat. Gen., 18 September 2005 [e-pub ahead of print]. doi:10.1038/ng1642
Citation: M. Leslie, Plumbing Problem. Sci. Aging Knowl. Environ. 2005 (38), nf75 (2005).

Science of Aging Knowledge Environment. ISSN 1539-6150