Nanomaterials go head-to-head with fat cells

The discovery of a treatment that shrinks fat cells in mice could eventually help the 40 percent of Americans who are obese. 

Obesity, defined as a body mass index over 30, is a serious condition that increases the risk of heart disease, high blood pressure, diabetes, and even some cancers. Given the extent of the obesity pandemic, researchers are scrambling to develop novel treatments. Weight loss surgery and medication can treat obesity, but both come with drawbacks. A new approach recently developed at Columbia University could bolster treatment options, but experts caution that it’s a long road toward clinical success.

Scientists at Columbia Engineering and Columbia University Irving Medical Center discovered that a positively charged nanoparticle called PAMAM generation 3 (P-G3) can shrink unhealthy fat cells. Publishing their findings in Nature Nanotechnology on Dec. 1, they demonstrated P-G3’s ability to target visceral fat, the network of tissues surrounding the stomach, liver, and intestines, in obese mice.

Obesity is caused by excess growth of white adipose tissue. Adipose tissue, or more simply body fat, comes in two forms: white fat stores energy, while brown fat generates heat. The extracellular matrix—a framework of nutrients surrounding and supporting cells—of white fat cells is known to be negatively charged.

Led by Li Qiang and Kam Leong, the team at Columbia hypothesized that a positively charged nanomaterial could leverage the negatively charged extracellular matrix to bind to adipose tissue. They injected P-G3 into obese mice with positive results.

P-G3 also inhibited lipid storage in white fat cells, preventing them from expanding to an unhealthy size. The inhibition of fat cell mass directly correlated to weight loss, with the mice losing 20 percent of their body fat after six weeks of P-G3 treatment. “Science gave us a huge surprise, in a good way,” said Li Qiang in an email to WORLD. “Cationic nanomaterial itself caused a strong reduction of fat.”

David Sarwer, director of the Center for Obesity Research and Education at Temple University’s College of Public Health, thought the study’s results were encouraging. But Sarwer cautioned that research done in animal models doesn’t always translate to humans. And even if it does in this instance, it could take years before a safe and effective treatment is available. “While this study is very exciting and interesting, we’ve got a long way to go until it becomes part of the conversation and a viable treatment for obesity in humans,” he said.

Philipp Scherer, director of the Touchstone Diabetes Center at UT Southwestern Medical Center, noted the study was right to focus on adipose tissue. He said there is a growing consensus in obesity research that fat tissue is the source of obesity and associated metabolic diseases. “It begins and it ends with the fat cell and its functionality,” he said.

Scherer explained that it can be difficult to deliver treatment to fat cells. The study, in his opinion, is interesting because it showed that a nanoparticle can selectively rejuvenate fat cells. He agreed with Sarwer that the treatment won’t be available to humans soon, and emphasized the need to prove that the nanomaterials aren’t toxic.

Sarwer and Scherer also agreed that bariatric surgery is the best existing treatment for obesity and its comorbidities. But Sarwer said that while most health insurance plans will cover the cost, bariatric surgery is underutilized in part because many people are challenged to complete the insurance-mandated preoperative program, which can take months to finish. Scherer pointed out that there simply aren’t enough surgeons to operate on 40 percent of the population.

That’s where medication comes into play. In 2021, the FDA approved a semaglutide sold under the name Wegovy for chronic weight management. Wegovy mimics an appetite-decreasing hormone to produce dramatic results, with a reported average weight loss of 15 percent after 68 weeks of treatment. As Scherer underlined, any drug developed using P-G3 must be competitive with existing obesity drugs.

Dr. Ken Yew, a family medicine physician in La Crosse, Wis., and a member of the Christian Medical and Dental Associations, described obesity as a consequence of living in a fallen world. In addition to the physiological factors already mentioned, Yew highlighted both individuals’ poor stewardship of their bodies and environmental factors, such as increased availability of unhealthy processed foods or being born to obese parents, as contributing to the problem.

Yew sees value in obesity research but expressed some reservations. While medical interventions can be helpful, he’s wary of instant fixes that can put a patient’s health at risk or eliminate personal responsibility.