Fat tissue is vascularized, much like a tumor, and growth of fat tissue is highly dependent on the tissue's ability to build new blood vessels—a phenomenon called angiogenesis. Inhibiting adipose angiogenesis—essentially "starving" fat tissue—can reverse the effects of a high-fat diet in mice and rats.
The team treated lean and obese mice and rats with the proapoptotic peptide for periods of four or 27 days. They measured energy intake and expenditure daily in all animals—some on low-fat diets, others on high-fat diets. The team found that the peptide completely reversed high-fat-diet-induced obesity in already obese mice and also reduced body weight in the mice and rats placed on high-fat diets. No changes were recorded in animals on low-fat diets.
Fat loss was occurring without major changes to energy expenditure, but with reduced
food intake. The authors noted that there were no signs of illness with this treatment and results were independent of the actions of the appetite-controlling hormone leptin.
"The body is extremely efficient at controlling energy balance," says Randy Seeley, a professor in UC's internal medicine department.
"Think of fat tissue like a bathtub. To keep the amount of water the same, you have to make sure that the speed of the water coming in and the water going out match. If the water is coming in faster than the water is going out, eventually you have to build a bigger bathtub. Obesity is the same."
"People who eat more calories than they burn have to build a bigger fat tissue 'bathtub,' and building new blood vessels is crucial to building this bigger bathtub. For each additional pound of fat tissue, you need to build a mile of blood vessels. What we found is that if we can target these fat tissue blood vessels, animals eat less and lose weight as their 'bathtubs' get smaller."
"These experiments indicate that there is a novel system that informs our brains about the size of our fat tissue 'bathtubs' and can influence how much we eat," says Seeley. "The findings highlight the ability to provide new therapeutic strategies for obesity based on these dynamics
of blood vessels in our fat tissue." The next step is to figure out the important signals that come from fat that cause the weight loss.