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Leaky Lymph May Feed Obesity -- St. Jude Scientist Directed Study, First to Suggest Connection

Posted on: Saturday, 15 October 2005, 12:00 CDT

By Mary Powers powers@commercialappealcom

Add a leaky lymphatic system to factors that might contribute to adult obesity.

That's the conclusion of researchers studying mice bred with a genetic defect that gives rise to a leaky lymphatic system, the body's drainage network that aids cancer's spread. As adults, about 90 percent of those mice became obese. Although they didn't eat more than the normal mice, typically they were 30 to 40 percent heavier.

"Are there patients with this lymphatic defect? It is probably very likely. There are forms of obesity for which there is no known cause," said Dr. Guillermo Oliver, the St. Jude Children's Research Hospital scientist who directed the study. The work was published in a recent issue of the scientific journal Nature Genetics. It involved investigators at St. Jude, the University of Arizona and a pharmaceutical company.

Nearly 23 percent of American adults are obese, meaning they weigh at least 20 percent more than the recommended amount.

For most, the problem is too many calories and too little exercise. But for some, the cause is more complex and includes specific inherited mistakes.

This study is the first suggesting obesity could arise from a malfunctioning lymphatic system.

Writing in the same issue of Nature Genetics, three Belgium scientists noted that the findings were "of enormous relevance" and represented a "major paradigm shift" in understanding and possibly combating obesity.

"If true, considerable effort could be exerted to identify effective therapeutic strategies" to address the problems, including strategies for repairing the lymph system or blocking factors that promoted fat accumulation, they wrote. The commentary came from researchers affiliated with the Center for Transgene Technology and Gene Therapy at the Flanders Interuniversity Institute for Biotechnology.

Oliver's research focus is genetics and organ development, not obesity.

In 1997, his research team published the first evidence the gene Prox1 carried instructions that directed development of the whole lymphatic system.

Like the circulatory system that carries blood, the lymphatic system is a network of large and small vessels radiating throughout the body carrying fluid called lymph. The system is crucial for maintaining the body's proper fluid balance. It also plays a role in fat absorption, the disease-fighting immune system and cancer's spread.

Oliver's team demonstrated that without at least one working copy of the gene, the lymphatic system can't develop properly.

Even with a single copy of Prox1, many mice didn't survive. Nearly all of those who did became obese as they matured. "If we provided a high fat diet, they gained more weight and they gained it faster," Oliver said.

Researchers noted the fat cells accumulated in areas where lymph from the faulty lymphatic system was leaking into tissue. The cells were larger than normal fat cells because they stored more fatty acids, triglycerides and other lipids.

Two additional studies strengthened the link.

Researchers reported that when certain cells growing in the lab were given lymph from the affected mice they became fat cells. And, when researchers removed the Prox1 gene just from the developing lymphatic system the mice still became fat.

It's unclear what in the lymph is driving the process, Oliver said.

"Our findings might encourage physicians to consider that at least some of their obese patients might be suffering from a problem that can't be solved by eating less and exercising more," he said.

- Mary Powers: 529-2383

Source: Commercial Appeal, The

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