Major obesity advance takes out targeted fat depots anywhere in the body

2022-12-01

The fat cells of an elite athlete can appear quite different to those in an obese subject, and technologies that make one function more like the other could unlock powerful new therapies for the condition. Scientists are reporting an exciting advance in this field, demonstrating how positively-charged nanomaterials can be injected into unhealthy fat to return it to a healthy state, laying the foundation for treatments that selectively target fat depots anywhere in the body.

Led by scientists at Columbia University, the research was published across two papers and centers on the different functions fat cells can take on in the human body, and the difference between healthy fat metabolism and unhealthy fat formation. Fat cells store energy in the form of lipids, but when they’re tasked with taking on too much, they start to grow large and undergo changes to specific genes, ultimately leading to obesity.

The research team set out to remodel these fat cells rather than simply destroy them, and have found success using a positively charged nanomaterial called PAMAM generation 3 (P-G3). The scientists were inspired to deploy P-G3 against fat cells after finding that some fat tissue contains a negatively charged extracellular matrix (ECM), the support structure for the cells. This raised the possibility that the ECM could act as a transport system for positively charged molecules.

So, the team injected P-G3 into obese mice and indeed found that it spread rapidly throughout the fat tissue. They were surprised to find, however, that the nanomaterial had the effect of shutting down the lipid storage function of the fat cells, effectively returning them to a younger, healthier state. The mice lost weight as a result.

“With P-G3, fat cells can still be fat cells, but they can’t grow up,” said study author Kam Leon. “Our studies highlight an unexpected strategy to treat visceral adiposity and suggest a new direction of exploring cationic nanomaterials for treating metabolic diseases.”

While the nanomaterial had the effect of neutralizing the lipid storage of the fat cells, it still allowed them to carry out their other functions, and even promoted the formation of new fat cells. The effect was mice with smaller, younger and more metabolically healthy fat cells, like those seen in newborns and athletes. Promisingly, the scientists also demonstrated the technique on human fat biopsies, boding well for the path to clinical use.

What is unique about the technology is its potential to offer targeted treatment for obesity. Fat “depots,” as they’re called, tend to be spaced intermittently around the body rather than forming one continuous lump of flabby tissue, but treating them in a selective manner has proven challenging. The scientists imagine one day using their technique to tackle specific fat depots, such as a pot belly or double chin, in the same way Botox is used to target specific patches of skin.

“We’re very excited to discover that cationic charge is the secret to targeting adipose tissue,” said team leader Li Qiang. “Now we can shrink fat in a depot-specific manner – anywhere we want – and in a safe way without destroying fat cells. This is a major advance in treating obesity.”

Further, because obesity is a driver of so many adverse health effects, from diabetes, to cancer, to cardiovascular disease, the scientists believe the technology could become a powerful new platform to deliver drugs and gene therapy to select fat depots. This could see drugs previously proven unsafe when administered systemically repurposed for use in a targeted manner.

The research was published in the journals Nature Nanotechnology and Biomaterials.

New Atlas, 1 December 2022
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