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Could Obesity Be Fought With A Glaucoma Drug?

Scientists have been working on ways to turn unhealthy beige fat into energy burning brown fat to fight obesity. Yale University scientists claim to have found a target for preventing fat uptake at point of entry and a class of glaucoma drugs may help to accomplish the goal, as published in Science.

Dietary fats carry chylomicrons from the digestive system to the bloodstream, which are absorbed into cells through lymphatic lacteal vessels. It was found narrowing lacteal junctions could stop chylomicrons from entering tissues. Inhibiting production of vascular endothelial growth factor A had been shown in previous studies to block growth of lacteals that appeared to limit fat uptake, with exact mechanisms not being clear.

In this study model mice normally expressing 2 VEGF-A receptors: NRP1 and FLT1 were genetically modified to delete the 2 receptors in endothelial cells and were fed high fat diets for 8 weeks. It was observed the altered model mice did not gain weight while unaltered mice doubled in weight.

Typically lacteals have button like gaps along the lining which chylomicrons slip into the surrounding tissues of, in the altered mice gaps were narrower zipper shaped openings that made it hard for fat carrying chylomicrons to pass through.

According to the scientists FLT1 and NRP1 are decoy factors of VEGF-A signalling, when removed signalling is over activated. VEGF-A signalling activating agents are believed to be able to achieve the same results. Rho kinase inhibitor was found to induce lacteal junction zippering and helped to prevent fat absorption, ROCK inhibition is a well documented treatment path for glaucoma.

American University scientists discovered a reservoir of dormant stem cells within the body that may transform into healthy fat. CHRNA2 signalling pathway was been identified that helps turn white fat into brown fat that the scientists from American University and the University of Michigan have found nicotine can promote the process.

Lacteals are suggested by the scientists to be a possible targets for future obesity therapies, believing that such drugs targeting as ROCK already available should be tested for effects on lipid absorption and weight loss.

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