In the United States, obesity is a major contributor to health problems and death. Heart disease, cancer, stroke, and respiratory diseases—four leading causes of death—are all exacerbated by obesity. Bioengineering postdoc and first author Natalia Gonzalez Medina, with her principal investigator bioengineering professor Andrew Smith, wanted to find a better treatment that could be more effectively targeted to specific sites in the body. Their new treatment, outlined in a paper published in ACS Nano, potentially provides a superior way to lose weight by using nanoparticles to deliver an anti-inflammatory drug, called dexamethasone, directly into fatty tissue.
Written by Ben Libman
Traditional weight loss drugs function by reducing appetite or nutrient absorption. This new therapy reduces body weight without changing food intake by increasing the rate of fat metabolism.
The visual abstract from the paper, entitled "Weight Loss without Food Intake Suppression through Size-Dependent Retention of Anti-Inflammatory Nanomedicines," published in ACS Nano.
In the United States, obesity is a major contributor to health problems and death. Heart disease, cancer, stroke, and respiratory diseases—four leading causes of death—are all exacerbated by obesity.
The most common methods of treatment are surgery or the more recently developed class of GLP-1s. Both approaches, however, have major drawbacks. Surgery is invasive, dangerous, and requires significant time and resources. GLP-1s work by causing appetite suppression, which can have many serious side effects. As bioengineering postdoc and first author Natalia Gonzalez Medina explains, “Because GLP-1s function primarily by suppressing appetite, there are other risk factors such as malnutrition or deficiencies in vitamins, protein, or fiber.”
Medina and her principal investigator, bioengineering professor Andrew Smith, wanted to find a better treatment that could be more effectively targeted to specific sites in the body. Their new treatment, outlined in a paper published in ACS Nano, potentially provides a superior way to lose weight by using nanoparticles to deliver an anti-inflammatory drug, called dexamethasone, directly into fatty tissue. The drug is delivered using microscopic particles of a sugar called dextran, ensuring that the drug is delivered to where it will be the most effective.
The treatment produced substantial weight loss in mouse models. Mice treated with the largest dextran-drug (which was still only 30 nanometers across) lost 20% of their body weight without reducing their food intake. “Certainly the magnitude of weight loss and body fat reduction without changes in food intake was striking,” said professor Smith. “We previously performed similar studies using a diverse range of interventions and never observed this in rodent models of obesity.”
The researchers theorized the effect was caused by adipose tissue browning. Smith explains: “Browning is the conversion of fat-storing adipose tissue into fat-burning adipose tissue—the tissue becomes brown in color when viewed under a microscope. The cells change their machinery to decompose fat and convert a large amount of its energy into heat. This conversion to heat causes a loss in total fat and a reduction in body weight. Without browning, fat decomposition would simply generate another form of chemical energy, rather than releasing the energy as heat.”
“There are two potential benefits of this research,” explains Medina. “The first is that we have designed an option to address obesity and its comorbidities. The second is that we provided a way to target pharmaceutical drugs locally to adipose tissue.”
Smith’s lab is continuing to advance this research. Next, the team hopes to localize the effects, targeting specific areas of fat. Each step forward brings this research closer to helping patients in the real world, improving their health and quality of life.
“This is an immunotherapy,” explains Smith, “a broad class of drugs that is growing rapidly and uses the immune system to shift biology in diverse ways. Targeting macrophages, as we do here, is a new means of shifting the immune system in a highly controlled, localized, and potent way.”