St Jude researchers identify a cause of obesity

The findings suggest that the abnormal leakage of lymph fluid from the ruptured lymphatic vessels stimulates the accumulation of fat, particularly in regions of the body rich in lymphatics.

The lymphatic vasculature (system of capillaries and vessels) that drains lymph is essential for the immune response in inflammation, and is the main route for the spreading of metastatic tumors to the lymph nodes.

The St Jude investigators showed that removal of one of the two copies of the gene Prox1 disrupts normal development of the lymphatic vasculature, leading to leakage of lymph from ruptured lymphatic vessels, and subsequent obesity.

Specifically, the researchers found that fat cells near leaking lymphatic vessels under the skin and in the abdomen were significantly larger than normal, and therefore able to store more lipids (e.g., fatty acids and triglycerides, used as an energy source).

“This is the first such evidence in an in vivo model showing that defects in the integrity of the lymphatic vasculature could lead to adult obesity,” said Dr Guillermo Oliver, an associate member of the Genetics and Tumor Cell Biology Department at St Jude. “And therefore, this is the first model available for studying obesity linked to faulty lymphatic vessels. It will be an important tool for studying this novel form of adult-onset obesity, as well as diseases of lymphatic vessels, and eventually, extending those findings to humans.”